Difference between revisions of "MDS, MDS/MPN and MPN Tables: Recurrent Genomic Alterations Detected by Chromosomal Microarray"
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| − | '''Table 1 | + | '''Table 1 - Evidence for the Clinical Utility of Chromosomal Microarray (CMA) Testing in Myeloid Disorders Excluding Acute Myeloid Leukemia (Literature Review).''' Table derived from Kanagal-Shawanna et al., 2018 [PMID 30377088] with permission from Cancer Genetics. |
{| class="wikitable" | {| class="wikitable" | ||
|'''Disease''' | |'''Disease''' | ||
| Line 38: | Line 38: | ||
| | | | ||
|4q loss | |4q loss | ||
| − | |''TET2'' | + | |''[[TET2]]'' |
|Prognostic for poor survival | |Prognostic for poor survival | ||
|<ref name=":3" /><ref name=":8" /><ref name=":10">Jankowska AM, Szpurka H, Tiu RV, Makishima H, Afable M, Huh J, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood 2009;113:6403-10.[https://www.ncbi.nlm.nih.gov/pubmed/19372255]</ref><ref name=":11">Bacher U, Weissmann S, Kohlmann A, Schindela S, Alpermann T, Schnittger S, et al. TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele. Br J Haematol 2012;156:67-75.[https://www.ncbi.nlm.nih.gov/pubmed/22017486]</ref><ref name=":12">Kolquist KA, Schultz RA, Furrow A, Brown TC, Han JY, Campbell LJ, et al. Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes. Cancer Genet 2011;204:603-28.[https://www.sciencedirect.com/science/article/pii/S2210776211002973]</ref> | |<ref name=":3" /><ref name=":8" /><ref name=":10">Jankowska AM, Szpurka H, Tiu RV, Makishima H, Afable M, Huh J, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood 2009;113:6403-10.[https://www.ncbi.nlm.nih.gov/pubmed/19372255]</ref><ref name=":11">Bacher U, Weissmann S, Kohlmann A, Schindela S, Alpermann T, Schnittger S, et al. TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele. Br J Haematol 2012;156:67-75.[https://www.ncbi.nlm.nih.gov/pubmed/22017486]</ref><ref name=":12">Kolquist KA, Schultz RA, Furrow A, Brown TC, Han JY, Campbell LJ, et al. Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes. Cancer Genet 2011;204:603-28.[https://www.sciencedirect.com/science/article/pii/S2210776211002973]</ref> | ||
| Line 45: | Line 45: | ||
| | | | ||
|4q CN-LOH | |4q CN-LOH | ||
| − | |''TET2'' | + | |''[[TET2]]'' |
|Prognostic for poor survival | |Prognostic for poor survival | ||
|<ref name=":13">Gondek LP, Tiu R, O'Keefe CL, Sekeres MA, Theil KS, Maciejewski JP. Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML. Blood 2008;111:1534-42.[https://www.ncbi.nlm.nih.gov/pubmed/17954704]</ref><ref name=":3" /><ref name=":14">Heinrichs S, Kulkarni RV, Bueso-Ramos CE, Levine RL, Loh ML, Li C, et al. Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics. Leukemia 2009;23:1605-13.[https://www.nature.com/articles/leu200982]</ref><ref name=":8" /><ref name=":9" /><ref name=":1" /><ref name=":5" /><ref name=":15">Mohamedali AM, Smith AE, Gaken J, Lea NC, Mian SA, Westwood NB, et al. Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome. J Clin Oncol 2009;27:4002-6.[https://www.ncbi.nlm.nih.gov/pubmed/19528370]</ref><ref name=":16">Mohamedali A, Gaken J, Twine NA, Ingram W, Westwood N, Lea NC, et al. Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes. Blood 2007;110:3365-73.[https://www.ncbi.nlm.nih.gov/pubmed/17634407]</ref><ref name=":17">Flach J, Dicker F, Schnittger S, Schindela S, Kohlmann A, Haferlach T, et al. An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling. Leukemia 2011;25:713-8.[https://www.nature.com/articles/leu2010304]</ref><ref name=":18">Larsson N, Lilljebjorn H, Lassen C, Johansson B, Fioretos T. Myeloid malignancies with acquired trisomy 21 as the sole cytogenetic change are clinically highly variable and display a heterogeneous pattern of copy number alterations and mutations. Eur J Haematol 2012;88:136-43.[https://www.ncbi.nlm.nih.gov/pubmed/21933280]</ref> | |<ref name=":13">Gondek LP, Tiu R, O'Keefe CL, Sekeres MA, Theil KS, Maciejewski JP. Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML. Blood 2008;111:1534-42.[https://www.ncbi.nlm.nih.gov/pubmed/17954704]</ref><ref name=":3" /><ref name=":14">Heinrichs S, Kulkarni RV, Bueso-Ramos CE, Levine RL, Loh ML, Li C, et al. Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics. Leukemia 2009;23:1605-13.[https://www.nature.com/articles/leu200982]</ref><ref name=":8" /><ref name=":9" /><ref name=":1" /><ref name=":5" /><ref name=":15">Mohamedali AM, Smith AE, Gaken J, Lea NC, Mian SA, Westwood NB, et al. Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome. J Clin Oncol 2009;27:4002-6.[https://www.ncbi.nlm.nih.gov/pubmed/19528370]</ref><ref name=":16">Mohamedali A, Gaken J, Twine NA, Ingram W, Westwood N, Lea NC, et al. Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes. Blood 2007;110:3365-73.[https://www.ncbi.nlm.nih.gov/pubmed/17634407]</ref><ref name=":17">Flach J, Dicker F, Schnittger S, Schindela S, Kohlmann A, Haferlach T, et al. An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling. Leukemia 2011;25:713-8.[https://www.nature.com/articles/leu2010304]</ref><ref name=":18">Larsson N, Lilljebjorn H, Lassen C, Johansson B, Fioretos T. Myeloid malignancies with acquired trisomy 21 as the sole cytogenetic change are clinically highly variable and display a heterogeneous pattern of copy number alterations and mutations. Eur J Haematol 2012;88:136-43.[https://www.ncbi.nlm.nih.gov/pubmed/21933280]</ref> | ||
| Line 59: | Line 59: | ||
| | | | ||
|7q loss | |7q loss | ||
| − | |''CUX1, EZH2'' | + | |''[[CUX1]], [[EZH2]]'' |
|Prognostic for poor survival | |Prognostic for poor survival | ||
|<ref name=":3" /><ref name=":19" /><ref name=":23">Thiel A, Beier M, Ingenhag D, Servan K, Hein M, Moeller V, et al. Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance. Leukemia 2011;25:387-99.[https://www.ncbi.nlm.nih.gov/pubmed/21274003]</ref><ref name=":9" /><ref name=":24">Volkert S, Haferlach T, Holzwarth J, Zenger M, Kern W, Staller M, et al. Array CGH identifies copy number changes in 11% of 520 MDS patients with normal karyotype and uncovers prognostically relevant deletions. Leukemia 2016;30:257-60.[https://www.ncbi.nlm.nih.gov/pubmed/26392226]</ref><ref name=":25">Svobodova K, Zemanova Z, Lhotska H, Novakova M, Podskalska L, Belickova M, et al. Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes. Leuk Res 2016;42:7-12.[https://www.ncbi.nlm.nih.gov/pubmed/26851439]</ref><ref name=":16" /><ref name=":6" /><ref name=":17" /><ref name=":26">Babushok DV, Xie HM, Roth JJ, Perdigones N, Olson TS, Cockroft JD, et al. Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes. Br J Haematol 2014;164:73-82.[https://www.ncbi.nlm.nih.gov/pubmed/24116929]</ref><ref name=":27">Stevens-Kroef MJ, Hebeda KM, Verwiel ET, Kamping EJ, van Cleef PH, Kuiper RP, et al. Microarray-based genomic profiling and in situ hybridization on fibrotic bone marrow biopsies for the identification of numerical chromosomal abnormalities in myelodysplastic syndrome. Mol Cytogenet 2015;8:33.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447009/]</ref><ref name=":7" /><ref name=":28">Barresi V, Palumbo GA, Musso N, Consoli C, Capizzi C, Meli CR, et al. Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied patient during MDS progression to AML. Leuk Res 2010;34:1539-42.[https://www.ncbi.nlm.nih.gov/pubmed/20674974]</ref><ref name=":22" /> | |<ref name=":3" /><ref name=":19" /><ref name=":23">Thiel A, Beier M, Ingenhag D, Servan K, Hein M, Moeller V, et al. Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance. Leukemia 2011;25:387-99.[https://www.ncbi.nlm.nih.gov/pubmed/21274003]</ref><ref name=":9" /><ref name=":24">Volkert S, Haferlach T, Holzwarth J, Zenger M, Kern W, Staller M, et al. Array CGH identifies copy number changes in 11% of 520 MDS patients with normal karyotype and uncovers prognostically relevant deletions. Leukemia 2016;30:257-60.[https://www.ncbi.nlm.nih.gov/pubmed/26392226]</ref><ref name=":25">Svobodova K, Zemanova Z, Lhotska H, Novakova M, Podskalska L, Belickova M, et al. Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes. Leuk Res 2016;42:7-12.[https://www.ncbi.nlm.nih.gov/pubmed/26851439]</ref><ref name=":16" /><ref name=":6" /><ref name=":17" /><ref name=":26">Babushok DV, Xie HM, Roth JJ, Perdigones N, Olson TS, Cockroft JD, et al. Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes. Br J Haematol 2014;164:73-82.[https://www.ncbi.nlm.nih.gov/pubmed/24116929]</ref><ref name=":27">Stevens-Kroef MJ, Hebeda KM, Verwiel ET, Kamping EJ, van Cleef PH, Kuiper RP, et al. Microarray-based genomic profiling and in situ hybridization on fibrotic bone marrow biopsies for the identification of numerical chromosomal abnormalities in myelodysplastic syndrome. Mol Cytogenet 2015;8:33.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447009/]</ref><ref name=":7" /><ref name=":28">Barresi V, Palumbo GA, Musso N, Consoli C, Capizzi C, Meli CR, et al. Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied patient during MDS progression to AML. Leuk Res 2010;34:1539-42.[https://www.ncbi.nlm.nih.gov/pubmed/20674974]</ref><ref name=":22" /> | ||
| Line 73: | Line 73: | ||
| | | | ||
|11q CN-LOH | |11q CN-LOH | ||
| − | |''CBL'' | + | |''[[CBL]]'' |
|Prognostic/ recurrent | |Prognostic/ recurrent | ||
|<ref name=":13" /><ref name=":3" /><ref name=":19" /><ref name=":4" /> <ref name=":1" /><ref name=":5" /><ref name=":17" /><ref name=":7" /> | |<ref name=":13" /><ref name=":3" /><ref name=":19" /><ref name=":4" /> <ref name=":1" /><ref name=":5" /><ref name=":17" /><ref name=":7" /> | ||
| Line 80: | Line 80: | ||
| | | | ||
|12p loss | |12p loss | ||
| − | |''ETV6'' | + | |''[[ETV6]]'' |
|Recurrent | |Recurrent | ||
|<ref name=":3" /><ref name=":14" /><ref name=":9" /><ref name=":24" /><ref name=":12" /> | |<ref name=":3" /><ref name=":14" /><ref name=":9" /><ref name=":24" /><ref name=":12" /> | ||
| Line 87: | Line 87: | ||
| | | | ||
|13q loss | |13q loss | ||
| − | |''?RB1'' | + | |''?[[RB1]]'' |
|Recurrent | |Recurrent | ||
|<ref name=":3" /><ref name=":8" /><ref name=":24" /><ref name=":1" /><ref name=":7" /> | |<ref name=":3" /><ref name=":8" /><ref name=":24" /><ref name=":1" /><ref name=":7" /> | ||
| Line 94: | Line 94: | ||
| | | | ||
|17p loss | |17p loss | ||
| − | |''TP53'' | + | |''[[TP53]]'' |
|Recurrent | |Recurrent | ||
|<ref name=":3" /><ref name=":9" /><ref name=":30">Zhang R, Kim YM, Wang X, Li Y, Lu X, Sternenberger AR, et al. Genomic Copy Number Variations in the Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients with del(5q) and/or -7/del(7q). Int J Med Sci 2015;12:719-26.[https://www.ncbi.nlm.nih.gov/pubmed/26392809]</ref><ref name=":12" /><ref name=":27" /> | |<ref name=":3" /><ref name=":9" /><ref name=":30">Zhang R, Kim YM, Wang X, Li Y, Lu X, Sternenberger AR, et al. Genomic Copy Number Variations in the Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients with del(5q) and/or -7/del(7q). Int J Med Sci 2015;12:719-26.[https://www.ncbi.nlm.nih.gov/pubmed/26392809]</ref><ref name=":12" /><ref name=":27" /> | ||
| Line 101: | Line 101: | ||
| | | | ||
|17p CN-LOH | |17p CN-LOH | ||
| − | |''TP53'' | + | |''[[TP53]]'' |
|Diagnostic for advanced MDS/sAML | |Diagnostic for advanced MDS/sAML | ||
|<ref name=":8" /><ref name=":9" /><ref name=":1" /><ref name=":5" /><ref name=":25" /> | |<ref name=":8" /><ref name=":9" /><ref name=":1" /><ref name=":5" /><ref name=":25" /> | ||
| Line 115: | Line 115: | ||
| | | | ||
|21q CN-LOH or deletion | |21q CN-LOH or deletion | ||
| − | |''RUNX1'' | + | |''[[RUNX1]]'' |
|Prognostic for progression to AML | |Prognostic for progression to AML | ||
|<ref name=":3" /><ref name=":23" /><ref name=":24" /><ref name=":12" /><ref name=":6" /><ref name=":29" /> | |<ref name=":3" /><ref name=":23" /><ref name=":24" /><ref name=":12" /><ref name=":6" /><ref name=":29" /> | ||
| Line 122: | Line 122: | ||
|73%/NA | |73%/NA | ||
|4q CN-LOH | |4q CN-LOH | ||
| − | |''TET2'' | + | |''[[TET2]]'' |
|Recurrent | |Recurrent | ||
|<ref name=":13" /><ref name=":33">Palomo L, Xicoy B, Garcia O, Mallo M, Adema V, Cabezon M, et al. Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases. Am J Hematol 2016;91:185-92.[https://www.ncbi.nlm.nih.gov/pubmed/26509444]</ref><ref name=":10" /><ref name=":17" /><ref name=":32" /> | |<ref name=":13" /><ref name=":33">Palomo L, Xicoy B, Garcia O, Mallo M, Adema V, Cabezon M, et al. Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases. Am J Hematol 2016;91:185-92.[https://www.ncbi.nlm.nih.gov/pubmed/26509444]</ref><ref name=":10" /><ref name=":17" /><ref name=":32" /> | ||
| Line 129: | Line 129: | ||
| | | | ||
|7q CN-LOH | |7q CN-LOH | ||
| − | |''Likely CUX1'' | + | |''Likely [[CUX1]]'' |
|Recurrent | |Recurrent | ||
|<ref name=":13" /><ref name=":33" /><ref name=":5" /><ref name=":6" /><ref name=":17" /> | |<ref name=":13" /><ref name=":33" /><ref name=":5" /><ref name=":6" /><ref name=":17" /> | ||
| Line 136: | Line 136: | ||
| | | | ||
|11q CN-LOH | |11q CN-LOH | ||
| − | |''CBL'' | + | |''[[CBL]]'' |
|Recurrent | |Recurrent | ||
|<ref name=":13" /><ref name=":33" /><ref name=":10" /><ref name=":5" /><ref name=":34">Gondek LP, Dunbar AJ, Szpurka H, McDevitt MA, Maciejewski JP. SNP array karyotyping allows for the detection of uniparental disomy and cryptic chromosomal abnormalities in MDS/MPD-U and MPD. PLoS One 2007;2:e1225. [https://www.ncbi.nlm.nih.gov/pubmed/18030353]</ref> | |<ref name=":13" /><ref name=":33" /><ref name=":10" /><ref name=":5" /><ref name=":34">Gondek LP, Dunbar AJ, Szpurka H, McDevitt MA, Maciejewski JP. SNP array karyotyping allows for the detection of uniparental disomy and cryptic chromosomal abnormalities in MDS/MPD-U and MPD. PLoS One 2007;2:e1225. [https://www.ncbi.nlm.nih.gov/pubmed/18030353]</ref> | ||
| Line 145: | Line 145: | ||
| | | | ||
|Recurrent | |Recurrent | ||
| − | |<ref>Singh NR, Morris CM, Koleth M, Wong K, Ward CM, Stevenson WS. Polyploidy in myelofibrosis: analysis by cytogenetic and SNP array indicates association with advancing disease. Mol Cytogenet 2013;6:59.[https://www.ncbi.nlm.nih.gov/pubmed/24341401]</ref><ref name=":37">Hahm C, Huh HJ, Mun YC, Seong CM, Chung WS, Huh J. Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression. Int J Lab Hematol 2015;37:181-9.[https://www.ncbi.nlm.nih.gov/pubmed/24845343]</ref> | + | |<ref name=":49">Singh NR, Morris CM, Koleth M, Wong K, Ward CM, Stevenson WS. Polyploidy in myelofibrosis: analysis by cytogenetic and SNP array indicates association with advancing disease. Mol Cytogenet 2013;6:59.[https://www.ncbi.nlm.nih.gov/pubmed/24341401]</ref><ref name=":37">Hahm C, Huh HJ, Mun YC, Seong CM, Chung WS, Huh J. Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression. Int J Lab Hematol 2015;37:181-9.[https://www.ncbi.nlm.nih.gov/pubmed/24845343]</ref> |
|- | |- | ||
| | | | ||
| | | | ||
|4q loss | |4q loss | ||
| − | |''TET2'' | + | |''[[TET2]]'' |
|Prognostic for progression to AML | |Prognostic for progression to AML | ||
|<ref name=":11" /><ref name=":38">Klampfl T, Harutyunyan A, Berg T, Gisslinger B, Schalling M, Bagienski K, et al. Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression. Blood 2011;118:167-76.[https://www.ncbi.nlm.nih.gov/pubmed/21531982]</ref> | |<ref name=":11" /><ref name=":38">Klampfl T, Harutyunyan A, Berg T, Gisslinger B, Schalling M, Bagienski K, et al. Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression. Blood 2011;118:167-76.[https://www.ncbi.nlm.nih.gov/pubmed/21531982]</ref> | ||
| Line 157: | Line 157: | ||
| | | | ||
|9p CN-LOH | |9p CN-LOH | ||
| − | |''JAK2'' | + | |''[[JAK2]]'' |
|Predictive for JAK2 inhibitors; Prognostic for PV progression to MF | |Predictive for JAK2 inhibitors; Prognostic for PV progression to MF | ||
|<ref name=":35">Rumi E, Harutyunyan A, Elena C, Pietra D, Klampfl T, Bagienski K, et al. Identification of genomic aberrations associated with disease transformation by means of high-resolution SNP array analysis in patients with myeloproliferative neoplasm. Am J Hematol 2011;86:974-9.[https://www.ncbi.nlm.nih.gov/pubmed/21953568]</ref><ref name=":34" /><ref name=":35" /><ref name=":37" /><ref name=":39">Stegelmann F, Bullinger L, Griesshammer M, Holzmann K, Habdank M, Kuhn S, et al. High-resolution single-nucleotide polymorphism array-profiling in myeloproliferative neoplasms identifies novel genomic aberrations. Haematologica 2010;95:666-9.[https://www.ncbi.nlm.nih.gov/pubmed/20015882]</ref> | |<ref name=":35">Rumi E, Harutyunyan A, Elena C, Pietra D, Klampfl T, Bagienski K, et al. Identification of genomic aberrations associated with disease transformation by means of high-resolution SNP array analysis in patients with myeloproliferative neoplasm. Am J Hematol 2011;86:974-9.[https://www.ncbi.nlm.nih.gov/pubmed/21953568]</ref><ref name=":34" /><ref name=":35" /><ref name=":37" /><ref name=":39">Stegelmann F, Bullinger L, Griesshammer M, Holzmann K, Habdank M, Kuhn S, et al. High-resolution single-nucleotide polymorphism array-profiling in myeloproliferative neoplasms identifies novel genomic aberrations. Haematologica 2010;95:666-9.[https://www.ncbi.nlm.nih.gov/pubmed/20015882]</ref> | ||
| Line 178: | Line 178: | ||
|21-24%/NA | |21-24%/NA | ||
|17p loss | |17p loss | ||
| − | |''TP53'' | + | |''[[TP53]]'' |
|Recurrent, progression, associated with TKI resistance | |Recurrent, progression, associated with TKI resistance | ||
|<ref name=":41">Nowak D, Ogawa S, Muschen M, Kato M, Kawamata N, Meixel A, et al. SNP array analysis of tyrosine kinase inhibitor-resistant chronic myeloid leukemia identifies heterogeneous secondary genomic alterations. Blood 2010;115:1049-53.[https://www.ncbi.nlm.nih.gov/pubmed/19965645]</ref><ref name=":42">Boultwood J, Perry J, Zaman R, Fernandez-Santamaria C, Littlewood T, Kusec R, et al. High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression. Leukemia 2010;24:1139-45.[https://www.ncbi.nlm.nih.gov/pubmed/20410925]</ref> | |<ref name=":41">Nowak D, Ogawa S, Muschen M, Kato M, Kawamata N, Meixel A, et al. SNP array analysis of tyrosine kinase inhibitor-resistant chronic myeloid leukemia identifies heterogeneous secondary genomic alterations. Blood 2010;115:1049-53.[https://www.ncbi.nlm.nih.gov/pubmed/19965645]</ref><ref name=":42">Boultwood J, Perry J, Zaman R, Fernandez-Santamaria C, Littlewood T, Kusec R, et al. High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression. Leukemia 2010;24:1139-45.[https://www.ncbi.nlm.nih.gov/pubmed/20410925]</ref> | ||
| Line 204: | Line 204: | ||
|} | |} | ||
| − | '''Table 2 | + | AA, Aplastic anemia; BMFS, Bone Marrow Failure Syndrome; MDS, Myelodysplastic Syndrome; MDS/MPN, Myelodysplastic/ myeloproliferative Neoplasm; MPN, Myeloproliferative Neoplasm; CML, Chronic Myelogeneous Leukemia; sAML, secondary AML; TGA, Total genomic aberration; TKI, tyrosine kinase inhibitors. |
| + | |||
| + | ∗Recurrent indicates recurrent aberration with no established prognostic significance | ||
| + | |||
| + | |||
| + | '''Table 2 -''' '''A Comprehensive List of Copy Number Aberrations and CN-LOH of Known or Likely Clinical Significance in MDS Detected by CMA Testing (Literature Review).''' Table derived from Kanagal-Shawanna et al., 2018 [PMID 30377088] with permission from Cancer Genetics. | ||
{| class="wikitable" | {| class="wikitable" | ||
|'''Chromosome''' | |'''Chromosome''' | ||
| Line 219: | Line 224: | ||
|Gain | |Gain | ||
|1p36.33-p33 | |1p36.33-p33 | ||
| − | |''MPL'' | + | |''[[MPL]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 229: | Line 234: | ||
|CN-LOH | |CN-LOH | ||
|1p | |1p | ||
| − | |''MPL'' | + | |''[[MPL]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 247: | Line 252: | ||
|CN-LOH | |CN-LOH | ||
|2pter-2p13.3 | |2pter-2p13.3 | ||
| − | |''DNMT3A'' | + | |''[[DNMT3A]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 256: | Line 261: | ||
|CN-LOH | |CN-LOH | ||
|3q21.3-qter | |3q21.3-qter | ||
| − | |''MECOM, | + | |''[[MECOM]], [[GATA2]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 265: | Line 270: | ||
|Loss | |Loss | ||
|4q24 | |4q24 | ||
| − | |''TET2'' | + | |''[[TET2]]'' |
|T*** | |T*** | ||
|2 | |2 | ||
| Line 274: | Line 279: | ||
|CN-LOH | |CN-LOH | ||
|4q12-qter | |4q12-qter | ||
| − | |''TET2'' | + | |''[[TET2]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 292: | Line 297: | ||
|Loss | |Loss | ||
|5q | |5q | ||
| − | |''RPS14'' | + | |''[[RPS14]]'' |
|D, P (Good when isolated) | |D, P (Good when isolated) | ||
|1 | |1 | ||
| Line 301: | Line 306: | ||
|Loss | |Loss | ||
|7q | |7q | ||
| − | |''EZH2, CUX1'' | + | |''[[EZH2]], [[CUX1]]'' |
|D, P (Intermediate) | |D, P (Intermediate) | ||
|1 | |1 | ||
| Line 310: | Line 315: | ||
|CN-LOH | |CN-LOH | ||
|7q21.11-qter | |7q21.11-qter | ||
| − | |''EZH2, CUX1'' | + | |''[[EZH2]], [[CUX1]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 337: | Line 342: | ||
|Gain | |Gain | ||
|9p | |9p | ||
| − | |''JAK2'' | + | |''[[JAK2]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 346: | Line 351: | ||
|CN-LOH | |CN-LOH | ||
|9pter-p24.2 | |9pter-p24.2 | ||
| − | |''JAK2'' | + | |''[[JAK2]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 355: | Line 360: | ||
|Loss | |Loss | ||
|11q14.1-q24.3 | |11q14.1-q24.3 | ||
| − | |''CBL'' | + | |''[[CBL]]'' |
|D, P (Very Good) | |D, P (Very Good) | ||
|1 | |1 | ||
| Line 364: | Line 369: | ||
|CN-LOH | |CN-LOH | ||
|11q13.3-qter | |11q13.3-qter | ||
| − | |''CBL'' | + | |''[[CBL]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 373: | Line 378: | ||
|Gain (Trisomy and q-arm) | |Gain (Trisomy and q-arm) | ||
|11 / 11q | |11 / 11q | ||
| − | |''CBL'' | + | |''[[CBL]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 382: | Line 387: | ||
|Loss | |Loss | ||
|12p | |12p | ||
| − | |''ETV6'' | + | |''[[ETV6]]'' |
|D, P (Good) | |D, P (Good) | ||
|1 | |1 | ||
| Line 391: | Line 396: | ||
|CN-LOH | |CN-LOH | ||
|12pter-p11.23 | |12pter-p11.23 | ||
| − | |''ETV6'' | + | |''[[ETV6]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 400: | Line 405: | ||
|Loss | |Loss | ||
|13q | |13q | ||
| − | |''RB1'' | + | |''[[RB1]]'' |
|D, P (Intermediate) | |D, P (Intermediate) | ||
|2 | |2 | ||
| Line 409: | Line 414: | ||
|CN-LOH | |CN-LOH | ||
|13q12.3-qter | |13q12.3-qter | ||
| − | |''FLT3, RB1'' | + | |''[[FLT3]], [[RB1]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 427: | Line 432: | ||
|CN-LOH | |CN-LOH | ||
|14q24.2-qter | |14q24.2-qter | ||
| − | |''CHGA'' | + | |''[[CHGA]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 436: | Line 441: | ||
|Loss (Monosomy and q-arm) | |Loss (Monosomy and q-arm) | ||
|16 / 16q | |16 / 16q | ||
| − | |''CDH1'' | + | |''[[CDH1]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 445: | Line 450: | ||
|CN-LOH | |CN-LOH | ||
|16q22.1-qter | |16q22.1-qter | ||
| − | |''CDH1'' | + | |''[[CDH1]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 454: | Line 459: | ||
|Loss | |Loss | ||
|17p | |17p | ||
| − | |''TP53'' | + | |''[[TP53]]'' |
|P (Poor) | |P (Poor) | ||
|1 | |1 | ||
| Line 463: | Line 468: | ||
|CN-LOH | |CN-LOH | ||
|17pter-p11.2 | |17pter-p11.2 | ||
| − | |''TP53'' | + | |''[[TP53]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 472: | Line 477: | ||
|Loss | |Loss | ||
|17q11.2 | |17q11.2 | ||
| − | |''NF1'' | + | |''[[NF1]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 481: | Line 486: | ||
|CN-LOH | |CN-LOH | ||
|17q11.2-qter | |17q11.2-qter | ||
| − | |''SRSF2, NF1'' | + | |''[[SRSF2]], [[NF1]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 490: | Line 495: | ||
|CN-LOH | |CN-LOH | ||
|19pter-p13.11 | |19pter-p13.11 | ||
| − | |''DNMT1, | + | |''[[DNMT1]], [[PRDX2]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 499: | Line 504: | ||
|Loss | |Loss | ||
|19p13.13 | |19p13.13 | ||
| − | |''PRDX2'' | + | |''[[PRDX2]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 526: | Line 531: | ||
|Loss | |Loss | ||
|20q | |20q | ||
| − | |''ASXL1'' | + | |''[[ASXL1]]'' |
|P (Good)** | |P (Good)** | ||
|1 | |1 | ||
| Line 535: | Line 540: | ||
|CN-LOH | |CN-LOH | ||
|20q11.21-qter | |20q11.21-qter | ||
| − | |''ASXL1'' | + | |''[[ASXL1]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 544: | Line 549: | ||
|Loss | |Loss | ||
|21q22.12 | |21q22.12 | ||
| − | |''RUNX1'' | + | |''[[RUNX1]]'' |
|D, P (Poor) | |D, P (Poor) | ||
|2 | |2 | ||
| Line 553: | Line 558: | ||
|CN-LOH | |CN-LOH | ||
|21q21.1-qter | |21q21.1-qter | ||
| − | |''RUNX1'', ''U2AF1'' | + | |''[[RUNX1]]'', ''[[U2AF1]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 571: | Line 576: | ||
|CN-LOH | |CN-LOH | ||
|22q11.23-qter | |22q11.23-qter | ||
| − | |''MN1, | + | |''[[MN1]], [[SF3A1]], [[EP300]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
|<ref name=":3" /><ref name=":7" /> | |<ref name=":3" /><ref name=":7" /> | ||
|} | |} | ||
| − | '''Table 3 | + | |
| + | Legend: d- diagnostic significance; P-prognostic significance; T- therapeutic significance. Recurrent indicates recurrent aberration with no established prognostic significance. | ||
| + | |||
| + | ∗ Clinical significance based on WHO classification using IPSS-R<ref>{{Cite journal|last=Greenberg|first=Peter L.|last2=Tuechler|first2=Heinz|last3=Schanz|first3=Julie|last4=Sanz|first4=Guillermo|last5=Garcia-Manero|first5=Guillermo|last6=Solé|first6=Francesc|last7=Bennett|first7=John M.|last8=Bowen|first8=David|last9=Fenaux|first9=Pierre|date=2012|title=Revised international prognostic scoring system for myelodysplastic syndromes|url=https://www.ncbi.nlm.nih.gov/pubmed/22740453|journal=Blood|volume=120|issue=12|pages=2454–2465|doi=10.1182/blood-2012-03-420489|issn=1528-0020|pmc=4425443|pmid=22740453}}</ref><ref>{{Cite journal|last=Schanz|first=Julie|last2=Tüchler|first2=Heinz|last3=Solé|first3=Francesc|last4=Mallo|first4=Mar|last5=Luño|first5=Elisa|last6=Cervera|first6=José|last7=Granada|first7=Isabel|last8=Hildebrandt|first8=Barbara|last9=Slovak|first9=Marilyn L.|date=2012|title=New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge|url=https://www.ncbi.nlm.nih.gov/pubmed/22331955|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=30|issue=8|pages=820–829|doi=10.1200/JCO.2011.35.6394|issn=1527-7755|pmc=4874200|pmid=22331955}}</ref>. | ||
| + | |||
| + | <nowiki>**</nowiki> Isolated trisomy 8 or del(20q) are not diagnostic of MDS in the absence of morphologic findings of disease. | ||
| + | |||
| + | ∗∗∗ Potential marker for responsiveness to hypomethylating agents or DNA methyltransferase inhibitors<ref name=":50">{{Cite journal|last=Bejar|first=Rafael|last2=Lord|first2=Allegra|last3=Stevenson|first3=Kristen|last4=Bar-Natan|first4=Michal|last5=Pérez-Ladaga|first5=Albert|last6=Zaneveld|first6=Jacques|last7=Wang|first7=Hui|last8=Caughey|first8=Bennett|last9=Stojanov|first9=Petar|date=2014|title=TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients|url=https://www.ncbi.nlm.nih.gov/pubmed/25224413|journal=Blood|volume=124|issue=17|pages=2705–2712|doi=10.1182/blood-2014-06-582809|issn=1528-0020|pmc=4208285|pmid=25224413}}</ref><ref name=":51">{{Cite journal|last=Traina|first=F.|last2=Visconte|first2=V.|last3=Elson|first3=P.|last4=Tabarroki|first4=A.|last5=Jankowska|first5=A. M.|last6=Hasrouni|first6=E.|last7=Sugimoto|first7=Y.|last8=Szpurka|first8=H.|last9=Makishima|first9=H.|date=2014|title=Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms|url=https://www.ncbi.nlm.nih.gov/pubmed/24045501|journal=Leukemia|volume=28|issue=1|pages=78–87|doi=10.1038/leu.2013.269|issn=1476-5551|pmid=24045501}}</ref>. | ||
| + | |||
| + | |||
| + | '''Table 3''' '''-''' '''A Comprehensive List of Copy Number Aberrations and CN-LOH of Known or Likely Clinical Significance in MDS/MPN Detected by CMA Testing (Literature Review).''' Table derived from Kanagal-Shawanna et al., 2018 [PMID 30377088] with permission from Cancer Genetics. | ||
{| class="wikitable" | {| class="wikitable" | ||
|'''Chromosome''' | |'''Chromosome''' | ||
| Line 591: | Line 606: | ||
|CN-LOH | |CN-LOH | ||
|1p21.3 | |1p21.3 | ||
| − | |''MPL'' | + | |''[[MPL]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 600: | Line 615: | ||
|Loss | |Loss | ||
|4q24 | |4q24 | ||
| − | |''TET2'' | + | |''[[TET2]]'' |
|Recurrent<sup>**</sup> | |Recurrent<sup>**</sup> | ||
|2 | |2 | ||
| Line 609: | Line 624: | ||
|CN-LOH | |CN-LOH | ||
|4q12.4-qter | |4q12.4-qter | ||
| − | |''TET2'' | + | |''[[TET2]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 618: | Line 633: | ||
|Loss (Monosomy and q-arm) | |Loss (Monosomy and q-arm) | ||
|5 / 5q | |5 / 5q | ||
| − | |''RPS14'' | + | |''[[RPS14]]'' |
|P (Intermediate) | |P (Intermediate) | ||
|1 | |1 | ||
| Line 627: | Line 642: | ||
|Loss | |Loss | ||
|7q | |7q | ||
| − | |''EZH2, CUX1'' | + | |''[[EZH2]], [[CUX1]]'' |
|P (Poor) | |P (Poor) | ||
|1 | |1 | ||
| Line 636: | Line 651: | ||
|CN-LOH | |CN-LOH | ||
|7q21.11-qter | |7q21.11-qter | ||
| − | |''EZH2, CUX1'' | + | |''[[EZH2]], [[CUX1]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 654: | Line 669: | ||
|CN-LOH | |CN-LOH | ||
|9pter-p13.3 | |9pter-p13.3 | ||
| − | |''JAK2'' | + | |''[[JAK2]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 663: | Line 678: | ||
|CN-LOH | |CN-LOH | ||
|11q13.2-qter | |11q13.2-qter | ||
| − | |''CBL'' | + | |''[[CBL]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 672: | Line 687: | ||
|Loss | |Loss | ||
|12p | |12p | ||
| − | |''ETV6'' | + | |''[[ETV6]]'' |
|P (Intermediate) | |P (Intermediate) | ||
|1 | |1 | ||
| Line 681: | Line 696: | ||
|Loss | |Loss | ||
|13q | |13q | ||
| − | |''RB1'' | + | |''[[RB1]]'' |
|P (Intermediate) | |P (Intermediate) | ||
|1 | |1 | ||
| Line 690: | Line 705: | ||
|CN-LOH | |CN-LOH | ||
|14q | |14q | ||
| − | |''CHGA'' | + | |''[[CHGA]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 699: | Line 714: | ||
|Loss | |Loss | ||
|17p | |17p | ||
| − | |''TP53'' | + | |''[[TP53]]'' |
|P (Poor)*** | |P (Poor)*** | ||
|1 | |1 | ||
| Line 708: | Line 723: | ||
|Loss | |Loss | ||
|20q | |20q | ||
| − | |''ASXL1'' | + | |''[[ASXL1]]'' |
|P (Intermediate) | |P (Intermediate) | ||
|2 | |2 | ||
| Line 717: | Line 732: | ||
|Gain | |Gain | ||
|21q22.12 | |21q22.12 | ||
| − | |''RUNX1'' | + | |''[[RUNX1]]'' |
|P (Intermediate) | |P (Intermediate) | ||
|2 | |2 | ||
| Line 726: | Line 741: | ||
|CN-LOH | |CN-LOH | ||
|21q22-qter | |21q22-qter | ||
| − | |''RUNX1'' | + | |''[[RUNX1]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
|<ref name=":33" /><ref name=":5" /> | |<ref name=":33" /><ref name=":5" /> | ||
|} | |} | ||
| − | + | ||
| + | Legend: d- diagnostic significance; P-prognostic significance; T- therapeutic significance. | ||
| − | MPN | + | Recurrent indicates recurrent aberration with no established significance. |
| + | |||
| + | ∗ Clinical significance based on International MDS/MPN Working Group recommendations<ref>{{Cite journal|last=Mughal|first=Tariq I.|last2=Cross|first2=Nicholas C. P.|last3=Padron|first3=Eric|last4=Tiu|first4=Ramon V.|last5=Savona|first5=Michael|last6=Malcovati|first6=Luca|last7=Tibes|first7=Raoul|last8=Komrokji|first8=Rami S.|last9=Kiladjian|first9=Jean-Jacques|date=2015|title=An International MDS/MPN Working Group's perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms|url=https://www.ncbi.nlm.nih.gov/pubmed/26341525|journal=Haematologica|volume=100|issue=9|pages=1117–1130|doi=10.3324/haematol.2014.114660|issn=1592-8721|pmc=4800699|pmid=26341525}}</ref>; No NCCN guidelines available. Low risk (normal, isolated –Y), Intermediate (others), High risk (+8, abnormal 7, complex). | ||
| + | |||
| + | ∗∗ Potential marker for responsiveness to hypomethylating agents or DNA methyltransferase inhibitors<ref name=":50" /><ref name=":51" />. | ||
| + | |||
| + | ∗∗∗ Haploinsufficiency of 17p as part of an isolated isochromosome may be a distinct disease entity with further increased risk of AML progression relative to 17p loss in a complex karyotype. | ||
| + | |||
| + | |||
| + | '''Table 4''' '''-''' '''A Comprehensive List of Copy Number Aberrations and CN-LOH of Known or Likely Clinical Significance in MPN Detected by CMA Testing (Literature Review).''' Table derived from Kanagal-Shawanna et al., 2018 [PMID 30377088] with permission from Cancer Genetics. | ||
{| class="wikitable" | {| class="wikitable" | ||
|Chromosome | |Chromosome | ||
| Line 748: | Line 773: | ||
|CN-LOH | |CN-LOH | ||
|1p21.3 | |1p21.3 | ||
| − | |''MPL'' | + | |''[[MPL]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 760: | Line 785: | ||
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| − | |<ref name=":35" /><ref name=": | + | |<ref name=":35" /><ref name=":49" /><ref name=":37" /> |
|- | |- | ||
|4 | |4 | ||
| Line 766: | Line 791: | ||
|Loss | |Loss | ||
|4q24 | |4q24 | ||
| − | |''TET2'' | + | |''[[TET2]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 775: | Line 800: | ||
|Loss | |Loss | ||
|5q | |5q | ||
| − | |''RPS14'' | + | |''[[RPS14]]'' |
|P (Poor) | |P (Poor) | ||
|1 | |1 | ||
| Line 784: | Line 809: | ||
|Loss | |Loss | ||
|6p23-22.3 | |6p23-22.3 | ||
| − | |''JARID2'' | + | |''[[JARID2]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| Line 793: | Line 818: | ||
|Loss | |Loss | ||
|7q | |7q | ||
| − | |''EZH2, CUX1'' | + | |''[[EZH2]], [[CUX1]]'' |
|P (Poor) | |P (Poor) | ||
|1 | |1 | ||
| Line 802: | Line 827: | ||
|CN-LOH | |CN-LOH | ||
|7q22.1-qter | |7q22.1-qter | ||
| − | |''EZH2, CUX1'' | + | |''[[EZH2]], [[CUX1]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| Line 820: | Line 845: | ||
|Gain | |Gain | ||
|9p | |9p | ||
| − | |''JAK2'' | + | |''[[JAK2]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| − | |<ref name=":35" /><ref name=": | + | |<ref name=":35" /><ref name=":49" /><ref name=":37" /> |
|- | |- | ||
|9 | |9 | ||
| Line 829: | Line 854: | ||
|CN-LOH | |CN-LOH | ||
|9pter-p13.3 | |9pter-p13.3 | ||
| − | |''JAK2'' | + | |''[[JAK2]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| − | |<ref name=":35" /><ref name=":34" /><ref name=": | + | |<ref name=":35" /><ref name=":34" /><ref name=":49" /><ref name=":37" /><ref name=":39" /> |
|- | |- | ||
|9 | |9 | ||
| Line 847: | Line 872: | ||
|Gain | |Gain | ||
|9q34 (+Ph) | |9q34 (+Ph) | ||
| − | |''ABL1'' | + | |''[[ABL1]]'' |
|Recurrent | |Recurrent | ||
|1 | |1 | ||
| Line 856: | Line 881: | ||
|CN-LOH | |CN-LOH | ||
|11q13.4-q25 | |11q13.4-q25 | ||
| − | |''CBL'' | + | |''[[CBL]]'' |
|Recurrent | |Recurrent | ||
|2 | |2 | ||
| − | |<ref name=":35" /><ref name=": | + | |<ref name=":35" /><ref name=":49" /> |
|- | |- | ||
|12 | |12 | ||
| Line 865: | Line 890: | ||
|Loss | |Loss | ||
|12p13.3-p12.2 | |12p13.3-p12.2 | ||
| − | |''ETV6'' | + | |''[[ETV6]]'' |
|P (Poor) | |P (Poor) | ||
|1 | |1 | ||
| Line 874: | Line 899: | ||
|Loss | |Loss | ||
|13q | |13q | ||
| − | |''RB1'' | + | |''[[RB1]]'' |
|Recurrent | |Recurrent | ||
|1 | |1 | ||
| Line 883: | Line 908: | ||
|CN-LOH | |CN-LOH | ||
|14q | |14q | ||
| − | |''CHGA'' | + | |''[[CHGA]]'' |
|Recurrent | |Recurrent | ||
|3 | |3 | ||
| − | |<ref name=":35" /><ref name=": | + | |<ref name=":35" /><ref name=":49" /><ref name=":37" /><ref name=":6" /> |
|- | |- | ||
|17 | |17 | ||
| Line 892: | Line 917: | ||
|Loss | |Loss | ||
|17p | |17p | ||
| − | |''TP53'' | + | |''[[TP53]]'' |
|P (Poor) | |P (Poor) | ||
|1 | |1 | ||
| Line 901: | Line 926: | ||
|Loss | |Loss | ||
|20q | |20q | ||
| − | |''ASXL1'' | + | |''[[ASXL1]]'' |
|Recurrent | |Recurrent | ||
|1 | |1 | ||
| Line 919: | Line 944: | ||
|Gain | |Gain | ||
|22q11.2 (+Ph) | |22q11.2 (+Ph) | ||
| − | |''BCR'' | + | |''[[BCR]]'' |
|Recurrent | |Recurrent | ||
|1 | |1 | ||
|<ref name=":41" /> | |<ref name=":41" /> | ||
|} | |} | ||
| + | Legend: d- diagnostic significance; P-prognostic significance; T- therapeutic significance. | ||
| + | |||
| + | Recurrent indicates recurrent aberration with no established significance. | ||
| + | |||
| + | ∗ Clinical significance based on NCCN guidelines<ref>{{Cite journal|last=Mesa|first=Ruben A.|last2=Jamieson|first2=Catriona|last3=Bhatia|first3=Ravi|last4=Deininger|first4=Michael W.|last5=Fletcher|first5=Christopher D.|last6=Gerds|first6=Aaron T.|last7=Gojo|first7=Ivana|last8=Gotlib|first8=Jason|last9=Gundabolu|first9=Krishna|date=2017|title=NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018|url=https://www.ncbi.nlm.nih.gov/pubmed/28982745|journal=Journal of the National Comprehensive Cancer Network: JNCCN|volume=15|issue=10|pages=1193–1207|doi=10.6004/jnccn.2017.0157|issn=1540-1413|pmid=28982745}}</ref>; For myelofibrosis, unfavorable [complex karyotype or sole or two abnormalities that include inv(3), 5/5q-, 7/7q-,+8, 11q23 rearrangement, 12p-, and (17q)]. | ||
| + | |||
| + | |||
<references /> | <references /> | ||
Latest revision as of 17:10, 30 April 2020
Table 1 - Evidence for the Clinical Utility of Chromosomal Microarray (CMA) Testing in Myeloid Disorders Excluding Acute Myeloid Leukemia (Literature Review). Table derived from Kanagal-Shawanna et al., 2018 [PMID 30377088] with permission from Cancer Genetics.
| Disease | Overall CMA detection rate | Key and unique
CMA aberrations |
Altered
gene(s) |
Impact | References |
| MDS | 28-83%
(Normal karyotype only: 11-39%) |
Total genomic alteration | Prognostic poor survival | [1][2][3][4][5] | |
| 1p CN-LOH | Prognostic for progression to AML | [6][7][8][9][10] | |||
| 1q gain | Recurrent | [6][11][12][10] | |||
| 4q loss | TET2 | Prognostic for poor survival | [6][11][13][14][15] | ||
| 4q CN-LOH | TET2 | Prognostic for poor survival | [16][6][17][11][12][3][8][18][19][20][21] | ||
| 5q loss | 5q loss “size” prognostic for progression to AML | [6][22][11][1][23][24][10][25] | |||
| 7q loss | CUX1, EZH2 | Prognostic for poor survival | [6][22][26][12][27][28][19][9][20][29][30][10][31][25] | ||
| 7q CN-LOH | Recurrent | [16][6][11][7][12][8][5][32][21] | |||
| 11q CN-LOH | CBL | Prognostic/ recurrent | [16][6][22][7] [3][8][20][10] | ||
| 12p loss | ETV6 | Recurrent | [6][17][12][27][15] | ||
| 13q loss | ?RB1 | Recurrent | [6][11][27][3][10] | ||
| 17p loss | TP53 | Recurrent | [6][12][33][15][30] | ||
| 17p CN-LOH | TP53 | Diagnostic for advanced MDS/sAML | [11][12][3][8][28] | ||
| 20q loss | Recurrent | [6][9][34][35][30][31][25] | |||
| 21q CN-LOH or deletion | RUNX1 | Prognostic for progression to AML | [6][26][27][15][9][32] | ||
| MDS/MPN | 73%/NA | 4q CN-LOH | TET2 | Recurrent | [16][36][13][20][35] |
| 7q CN-LOH | Likely CUX1 | Recurrent | [16][36][8][9][20] | ||
| 11q CN-LOH | CBL | Recurrent | [16][36][13][8][37] | ||
| MPN | >56%/NA | 1q gain | Recurrent | [38][39] | |
| 4q loss | TET2 | Prognostic for progression to AML | [14][40] | ||
| 9p CN-LOH | JAK2 | Predictive for JAK2 inhibitors; Prognostic for PV progression to MF | [41][37][41][39][42] | ||
| 14q CN-LOH | Presence of CNAs/CN-LOH prognostic for progression to AML | [41][39][9] | |||
| 20q loss | Recurrent | [41][43] | |||
| CML | 21-24%/NA | 17p loss | TP53 | Recurrent, progression, associated with TKI resistance | [44][45] |
| 2q CN-LOH | Diagnostic (only seen in BC) | [45] | |||
| 8p CN-LOH | Diagnostic (only seen in BC) | [45] | |||
| BMFS | 19% (AA) | 6p CN-LOH | ?HLA genes | Recurrent | [46][29][47] |
AA, Aplastic anemia; BMFS, Bone Marrow Failure Syndrome; MDS, Myelodysplastic Syndrome; MDS/MPN, Myelodysplastic/ myeloproliferative Neoplasm; MPN, Myeloproliferative Neoplasm; CML, Chronic Myelogeneous Leukemia; sAML, secondary AML; TGA, Total genomic aberration; TKI, tyrosine kinase inhibitors.
∗Recurrent indicates recurrent aberration with no established prognostic significance
Table 2 - A Comprehensive List of Copy Number Aberrations and CN-LOH of Known or Likely Clinical Significance in MDS Detected by CMA Testing (Literature Review). Table derived from Kanagal-Shawanna et al., 2018 [PMID 30377088] with permission from Cancer Genetics.
| Chromosome | Disease | Abnormality Type (Gain, Loss, CN-LOH) | Region | Relevant Genes (if known) | Clinical Significance* | Level of Evidence | References |
| 1 | MDS | Gain | 1p36.33-p33 | MPL | Recurrent | 3 | |
| 1 | MDS | CN-LOH | 1p | MPL | Recurrent | 2 | [6][7][8][9] |
| 1 | MDS | Gain | 1q | Recurrent | 2 | [6][11][12][10] | |
| 2 | MDS | CN-LOH | 2pter-2p13.3 | DNMT3A | Recurrent | 2 | [6][24][20][48] |
| 3 | MDS | CN-LOH | 3q21.3-qter | MECOM, GATA2 | Recurrent | 3 | [6][17][49][3][9] |
| 4 | MDS | Loss | 4q24 | TET2 | T*** | 2 | [6][26][11][13][14][27][15] |
| 4 | MDS | CN-LOH | 4q12-qter | TET2 | Recurrent | 2 | [16][6][17][11][50][12][8][18][19][20][21] |
| 5 | MDS | Gain | 5p | Suggestive of i(5p) with 5q del | Recurrent | 3 | [6] |
| 5 | MDS | Loss | 5q | RPS14 | D, P (Good when isolated) | 1 | [6][22][17][26][49][11][1][12][23][33][3][28][51][19][5][34][24][20][35][30][10][25][52] |
| 7 | MDS | Loss | 7q | EZH2, CUX1 | D, P (Intermediate) | 1 | [6][22][26][49][1][12][27][33][28][19][5][9][29][30][10][25] |
| 7 | MDS | CN-LOH | 7q21.11-qter | EZH2, CUX1 | Recurrent | 2 | [16][6][17][49][11][7][12][8][5][32][21] |
| 7 | MDS | Loss (Monosomy) | 7 | Whole Chromosome | D, P (Poor) | 1 | [33][28][19][20][29][30][10][31][25] |
| 8 | MDS | Gain (Trisomy) | 8 | Whole Chromosome | P (Intermediate)** | 1 | [6][11][12][33][15][5][9][34][53][29][30][25] |
| 9 | MDS | Gain | 9p | JAK2 | Recurrent | 3 | [6][12][15] |
| 9 | MDS | CN-LOH | 9pter-p24.2 | JAK2 | Recurrent | 2 | [6][2][3] |
| 11 | MDS | Loss | 11q14.1-q24.3 | CBL | D, P (Very Good) | 1 | [6][34] |
| 11 | MDS | CN-LOH | 11q13.3-qter | CBL | Recurrent | 2 | [16][6][22][7][3][8][20][10][31] |
| 11 | MDS | Gain (Trisomy and q-arm) | 11 / 11q | CBL | Recurrent | 3 | [6][17][1][12][20] |
| 12 | MDS | Loss | 12p | ETV6 | D, P (Good) | 1 | [6][17][12][27][15] |
| 12 | MDS | CN-LOH | 12pter-p11.23 | ETV6 | Recurrent | 2 | [3][20] |
| 13 | MDS | Loss | 13q | RB1 | D, P (Intermediate) | 2 | [6][11][3][10] |
| 13 | MDS | CN-LOH | 13q12.3-qter | FLT3, RB1 | Recurrent | 3 | [6][8][20] |
| 13 | MDS | Gain (Trisomy) | 13 | Whole Chromosome | Recurrent | 3 | [6] |
| 14 | MDS | CN-LOH | 14q24.2-qter | CHGA | Recurrent | 3 | [6][22][7][50][8] |
| 16 | MDS | Loss (Monosomy and q-arm) | 16 / 16q | CDH1 | Recurrent | 3 | [6][15][10] |
| 16 | MDS | CN-LOH | 16q22.1-qter | CDH1 | Recurrent | 3 | [6][32] |
| 17 | MDS | Loss | 17p | TP53 | P (Poor) | 1 | [6][12][33][51][15][5][30] |
| 17 | MDS | CN-LOH | 17pter-p11.2 | TP53 | Recurrent | 2 | [17][11][12][23][3][8][28][5] |
| 17 | MDS | Loss | 17q11.2 | NF1 | Recurrent | 3 | [27][15] |
| 17 | MDS | CN-LOH | 17q11.2-qter | SRSF2, NF1 | Recurrent | 2 | [6][49][7] |
| 19 | MDS | CN-LOH | 19pter-p13.11 | DNMT1, PRDX2 | Recurrent | 3 | [9][20] |
| 19 | MDS | Loss | 19p13.13 | PRDX2 | Recurrent | 3 | [1] |
| 19 | MDS | Gain (Trisomy) | 19 | Whole Chromosome | Recurrent | 2 | [6][9] |
| 20 | MDS | Gain | 20p | Suggestive of ider(20p) with 20q del | Recurrent | 3 | [6] |
| 20 | MDS | Loss | 20q | ASXL1 | P (Good)** | 1 | [6][11][1][51][5][9][34][35][32][30][31][25][22][12][19][43][54] |
| 20 | MDS | CN-LOH | 20q11.21-qter | ASXL1 | Recurrent | 2 | [5][32] |
| 21 | MDS | Loss | 21q22.12 | RUNX1 | D, P (Poor) | 2 | [6][17][26][11][27][33][15] |
| 21 | MDS | CN-LOH | 21q21.1-qter | RUNX1, U2AF1 | Recurrent | 2 | [6][7][5][21][52] |
| 21 | MDS | Gain (Trisomy) | 21 | Whole Chromosome | Recurrent | 2 | [6][12][30] |
| 22 | MDS | CN-LOH | 22q11.23-qter | MN1, SF3A1, EP300 | Recurrent | 3 | [6][10] |
Legend: d- diagnostic significance; P-prognostic significance; T- therapeutic significance. Recurrent indicates recurrent aberration with no established prognostic significance.
∗ Clinical significance based on WHO classification using IPSS-R[55][56].
** Isolated trisomy 8 or del(20q) are not diagnostic of MDS in the absence of morphologic findings of disease.
∗∗∗ Potential marker for responsiveness to hypomethylating agents or DNA methyltransferase inhibitors[57][58].
Table 3 - A Comprehensive List of Copy Number Aberrations and CN-LOH of Known or Likely Clinical Significance in MDS/MPN Detected by CMA Testing (Literature Review). Table derived from Kanagal-Shawanna et al., 2018 [PMID 30377088] with permission from Cancer Genetics.
| Chromosome | Disease | Abnormality Type (Gain, Loss, CN-LOH) | Region | Relevant Genes (if known) | Clinical Significance* | Level of Evidence | References |
| 1 | MDS/MPN | CN-LOH | 1p21.3 | MPL | Recurrent | 2 | [8] |
| 4 | MDS/MPN | Loss | 4q24 | TET2 | Recurrent** | 2 | [13] |
| 4 | MDS/MPN | CN-LOH | 4q12.4-qter | TET2 | Recurrent | 2 | [16][36][13][8][20][35] |
| 5 | MDS/MPN | Loss (Monosomy and q-arm) | 5 / 5q | RPS14 | P (Intermediate) | 1 | [13][59][23][37][39][24] |
| 7 | MDS/MPN | Loss | 7q | EZH2, CUX1 | P (Poor) | 1 | [16][37] |
| 7 | MDS/MPN | CN-LOH | 7q21.11-qter | EZH2, CUX1 | Recurrent | 2 | [16][36][8][9][20] |
| 8 | MDS/MPN | Gain (Trisomy) | 8 | Whole chromosome | P (Poor) | 1 | [39][20] |
| 9 | MDS/MPN | CN-LOH | 9pter-p13.3 | JAK2 | Recurrent | 2 | [8] |
| 11 | MDS/MPN | CN-LOH | 11q13.2-qter | CBL | Recurrent | 2 | [16][36][13][8] |
| 12 | MDS/MPN | Loss | 12p | ETV6 | P (Intermediate) | 1 | [36][59] |
| 13 | MDS/MPN | Loss | 13q | RB1 | P (Intermediate) | 1 | [37][39] |
| 14 | MDS/MPN | CN-LOH | 14q | CHGA | Recurrent | 3 | [8] |
| 17 | MDS/MPN | Loss | 17p | TP53 | P (Poor)*** | 1 | [39] |
| 20 | MDS/MPN | Loss | 20q | ASXL1 | P (Intermediate) | 2 | [37] |
| 21 | MDS/MPN | Gain | 21q22.12 | RUNX1 | P (Intermediate) | 2 | [36][13] |
| 21 | MDS/MPN | CN-LOH | 21q22-qter | RUNX1 | Recurrent | 2 | [36][8] |
Legend: d- diagnostic significance; P-prognostic significance; T- therapeutic significance.
Recurrent indicates recurrent aberration with no established significance.
∗ Clinical significance based on International MDS/MPN Working Group recommendations[60]; No NCCN guidelines available. Low risk (normal, isolated –Y), Intermediate (others), High risk (+8, abnormal 7, complex).
∗∗ Potential marker for responsiveness to hypomethylating agents or DNA methyltransferase inhibitors[57][58].
∗∗∗ Haploinsufficiency of 17p as part of an isolated isochromosome may be a distinct disease entity with further increased risk of AML progression relative to 17p loss in a complex karyotype.
Table 4 - A Comprehensive List of Copy Number Aberrations and CN-LOH of Known or Likely Clinical Significance in MPN Detected by CMA Testing (Literature Review). Table derived from Kanagal-Shawanna et al., 2018 [PMID 30377088] with permission from Cancer Genetics.
| Chromosome | Disease | Abnormality Type (Gain, Loss, CN-LOH) | Region | Relevant Genes (if known) | Clinical Significance* | Level of Evidence | Reference (PMID) |
| 1 | MPN | CN-LOH | 1p21.3 | MPL | Recurrent | 2 | [41] |
| 1 | MPN | Gain | 1q21.2-q32.1 | Recurrent | 2 | [41][38][39] | |
| 4 | MPN | Loss | 4q24 | TET2 | Recurrent | 2 | [14][40] |
| 5 | MPN | Loss | 5q | RPS14 | P (Poor) | 1 | [24] |
| 6 | MPN | Loss | 6p23-22.3 | JARID2 | Recurrent | 3 | [39][61] |
| 7 | MPN | Loss | 7q | EZH2, CUX1 | P (Poor) | 1 | [41] |
| 7 | MPN | CN-LOH | 7q22.1-qter | EZH2, CUX1 | Recurrent | 2 | [45] |
| 8 | MPN | Gain (Trisomy) | 8 | Whole chromosome | P (Poor) | 1 | [44] |
| 9 | MPN | Gain | 9p | JAK2 | Recurrent | 2 | [41][38][39] |
| 9 | MPN | CN-LOH | 9pter-p13.3 | JAK2 | Recurrent | 2 | [41][37][38][39][42] |
| 9 | CML | Loss | 9q34 | Recurrent | 3 | [62][44] | |
| 9 | CML | Gain | 9q34 (+Ph) | ABL1 | Recurrent | 1 | [44] |
| 11 | MPN | CN-LOH | 11q13.4-q25 | CBL | Recurrent | 2 | [41][38] |
| 12 | MPN | Loss | 12p13.3-p12.2 | ETV6 | P (Poor) | 1 | [45] |
| 13 | MPN | Loss | 13q | RB1 | Recurrent | 1 | [41] |
| 14 | MPN | CN-LOH | 14q | CHGA | Recurrent | 3 | [41][38][39][9] |
| 17 | MPN | Loss | 17p | TP53 | P (Poor) | 1 | [44][45][41] |
| 20 | MPN | Loss | 20q | ASXL1 | Recurrent | 1 | [41][43] |
| 22 | CML | Loss | 22q11.2 | Recurrent | 3 | [62][44] | |
| 22 | CML | Gain | 22q11.2 (+Ph) | BCR | Recurrent | 1 | [44] |
Legend: d- diagnostic significance; P-prognostic significance; T- therapeutic significance.
Recurrent indicates recurrent aberration with no established significance.
∗ Clinical significance based on NCCN guidelines[63]; For myelofibrosis, unfavorable [complex karyotype or sole or two abnormalities that include inv(3), 5/5q-, 7/7q-,+8, 11q23 rearrangement, 12p-, and (17q)].
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Starczynowski DT, Vercauteren S, Telenius A, Sung S, Tohyama K, Brooks-Wilson A, et al. High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival. Blood 2008;112:3412-24.[1]
- ↑ 2.0 2.1 Yeung CCS, McElhone S, Chen XY, Ng D, Storer BE, Deeg HJ, et al. Impact of copy neutral loss of heterozygosity and total genome aberrations on survival in myelodysplastic syndrome. Mod Pathol 2017.[2]
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 Arenillas L, Mallo M, Ramos F, Guinta K, Barragan E, Lumbreras E, et al. Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing. Genes Chromosomes Cancer 2013;52:1167-77.[3]
- ↑ Cluzeau T, Moreilhon C, Mounier N, Karsenti JM, Gastaud L, Garnier G, et al. Total genomic alteration as measured by SNP-array-based molecular karyotyping is predictive of overall survival in a cohort of MDS or AML patients treated with azacitidine. Blood Cancer J 2013;3:e155.[4]
- ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 Ganster C, Shirneshan K, Salinas-Riester G, Braulke F, Schanz J, Platzbecker U, et al. Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS. Leuk Res 2015;39:1079-87.[5]
- ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 6.19 6.20 6.21 6.22 6.23 6.24 6.25 6.26 6.27 6.28 6.29 6.30 6.31 6.32 6.33 6.34 6.35 6.36 6.37 6.38 6.39 6.40 6.41 6.42 6.43 6.44 6.45 Tiu RV, Gondek LP, O'Keefe CL, Elson P, Huh J, Mohamedali A, et al. Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies. Blood 2011;117:4552-60.[6]
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 Gondek LP, Haddad AS, O'Keefe CL, Tiu R, Wlodarski MW, Sekeres MA, et al. Detection of cryptic chromosomal lesions including acquired segmental uniparental disomy in advanced and low-risk myelodysplastic syndromes. Exp Hematol 2007;35:1728-38.[7]
- ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.15 8.16 8.17 8.18 8.19 8.20 Dunbar AJ, Gondek LP, O'Keefe CL, Makishima H, Rataul MS, Szpurka H, et al. 250K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies. Cancer Res 2008;68:10349-57.[8]
- ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 Sugimoto Y, Sekeres MA, Makishima H, Traina F, Visconte V, Jankowska A, et al. Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide. J Hematol Oncol 2012;5:4.[9]
- ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 10.12 10.13 Xu X, Johnson EB, Leverton L, Arthur A, Watson Q, Chang FL, et al. The advantage of using SNP array in clinical testing for hematological malignancies--a comparative study of three genetic testing methods. Cancer Genet 2013;206:317-26.[10]
- ↑ 11.00 11.01 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 11.11 11.12 11.13 11.14 11.15 11.16 Evans AG, Ahmad A, Burack WR, Iqbal MA. Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance. Mod Pathol 2016;29:1183-99.[11]
- ↑ 12.00 12.01 12.02 12.03 12.04 12.05 12.06 12.07 12.08 12.09 12.10 12.11 12.12 12.13 12.14 12.15 12.16 12.17 12.18 12.19 Hu Q, Chu Y, Song Q, Yao Y, Yang W, Huang S. The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China. Ann Hematol 2016;95:1241-8.[12]
- ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8 Jankowska AM, Szpurka H, Tiu RV, Makishima H, Afable M, Huh J, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood 2009;113:6403-10.[13]
- ↑ 14.0 14.1 14.2 14.3 Bacher U, Weissmann S, Kohlmann A, Schindela S, Alpermann T, Schnittger S, et al. TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele. Br J Haematol 2012;156:67-75.[14]
- ↑ 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 Kolquist KA, Schultz RA, Furrow A, Brown TC, Han JY, Campbell LJ, et al. Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes. Cancer Genet 2011;204:603-28.[15]
- ↑ 16.00 16.01 16.02 16.03 16.04 16.05 16.06 16.07 16.08 16.09 16.10 16.11 16.12 Gondek LP, Tiu R, O'Keefe CL, Sekeres MA, Theil KS, Maciejewski JP. Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML. Blood 2008;111:1534-42.[16]
- ↑ 17.0 17.1 17.2 17.3 17.4 17.5 17.6 17.7 17.8 17.9 Heinrichs S, Kulkarni RV, Bueso-Ramos CE, Levine RL, Loh ML, Li C, et al. Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics. Leukemia 2009;23:1605-13.[17]
- ↑ 18.0 18.1 Mohamedali AM, Smith AE, Gaken J, Lea NC, Mian SA, Westwood NB, et al. Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome. J Clin Oncol 2009;27:4002-6.[18]
- ↑ 19.0 19.1 19.2 19.3 19.4 19.5 19.6 Mohamedali A, Gaken J, Twine NA, Ingram W, Westwood N, Lea NC, et al. Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes. Blood 2007;110:3365-73.[19]
- ↑ 20.00 20.01 20.02 20.03 20.04 20.05 20.06 20.07 20.08 20.09 20.10 20.11 20.12 20.13 20.14 20.15 20.16 Flach J, Dicker F, Schnittger S, Schindela S, Kohlmann A, Haferlach T, et al. An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling. Leukemia 2011;25:713-8.[20]
- ↑ 21.0 21.1 21.2 21.3 21.4 Larsson N, Lilljebjorn H, Lassen C, Johansson B, Fioretos T. Myeloid malignancies with acquired trisomy 21 as the sole cytogenetic change are clinically highly variable and display a heterogeneous pattern of copy number alterations and mutations. Eur J Haematol 2012;88:136-43.[21]
- ↑ 22.0 22.1 22.2 22.3 22.4 22.5 22.6 22.7 22.8 Huh J, Jung CW, Kim HJ, Kim YK, Moon JH, Sohn SK, et al. Different characteristics identified by single nucleotide polymorphism array analysis in leukemia suggest the need for different application strategies depending on disease category. Genes Chromosomes Cancer 2013;52:44-55.[22]
- ↑ 23.0 23.1 23.2 23.3 Jerez A, Gondek LP, Jankowska AM, Makishima H, Przychodzen B, Tiu RV, et al. Topography, clinical, and genomic correlates of 5q myeloid malignancies revisited. J Clin Oncol 2012;30:1343-9.[23]
- ↑ 24.0 24.1 24.2 24.3 24.4 Stengel A, Kern W, Haferlach T, Meggendorfer M, Haferlach C. The 5q deletion size in myeloid malignancies is correlated to additional chromosomal aberrations and to TP53 mutations. Genes Chromosomes Cancer 2016;55:777-85. [24]
- ↑ 25.0 25.1 25.2 25.3 25.4 25.5 25.6 25.7 Kunze K, Gamerdinger U, Lessig-Owlanj J, Sorokina M, Brobeil A, Tur MK, et al. Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis. Pathol Res Pract 2014;210:369-76.[25]
- ↑ 26.0 26.1 26.2 26.3 26.4 26.5 Thiel A, Beier M, Ingenhag D, Servan K, Hein M, Moeller V, et al. Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance. Leukemia 2011;25:387-99.[26]
- ↑ 27.0 27.1 27.2 27.3 27.4 27.5 27.6 27.7 27.8 Volkert S, Haferlach T, Holzwarth J, Zenger M, Kern W, Staller M, et al. Array CGH identifies copy number changes in 11% of 520 MDS patients with normal karyotype and uncovers prognostically relevant deletions. Leukemia 2016;30:257-60.[27]
- ↑ 28.0 28.1 28.2 28.3 28.4 28.5 Svobodova K, Zemanova Z, Lhotska H, Novakova M, Podskalska L, Belickova M, et al. Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes. Leuk Res 2016;42:7-12.[28]
- ↑ 29.0 29.1 29.2 29.3 29.4 Babushok DV, Xie HM, Roth JJ, Perdigones N, Olson TS, Cockroft JD, et al. Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes. Br J Haematol 2014;164:73-82.[29]
- ↑ 30.0 30.1 30.2 30.3 30.4 30.5 30.6 30.7 30.8 30.9 Stevens-Kroef MJ, Hebeda KM, Verwiel ET, Kamping EJ, van Cleef PH, Kuiper RP, et al. Microarray-based genomic profiling and in situ hybridization on fibrotic bone marrow biopsies for the identification of numerical chromosomal abnormalities in myelodysplastic syndrome. Mol Cytogenet 2015;8:33.[30]
- ↑ 31.0 31.1 31.2 31.3 31.4 Barresi V, Palumbo GA, Musso N, Consoli C, Capizzi C, Meli CR, et al. Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied patient during MDS progression to AML. Leuk Res 2010;34:1539-42.[31]
- ↑ 32.0 32.1 32.2 32.3 32.4 32.5 Nowak D, Nolte F, Mossner M, Nowak V, Baldus CD, Hopfer O, et al. Genome-wide DNA-mapping of CD34+ cells from patients with myelodysplastic syndrome using 500K SNP arrays identifies significant regions of deletion and uniparental disomy. Exp Hematol 2009;37:215-24.[32]
- ↑ 33.0 33.1 33.2 33.3 33.4 33.5 33.6 Zhang R, Kim YM, Wang X, Li Y, Lu X, Sternenberger AR, et al. Genomic Copy Number Variations in the Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients with del(5q) and/or -7/del(7q). Int J Med Sci 2015;12:719-26.[33]
- ↑ 34.0 34.1 34.2 34.3 34.4 34.5 Vercauteren SM, Sung S, Starczynowski DT, Lam WL, Bruyere H, Horsman DE, et al. Array comparative genomic hybridization of peripheral blood granulocytes of patients with myelodysplastic syndrome detects karyotypic abnormalities. Am J Clin Pathol 2010;134:119-26. [34]
- ↑ 35.0 35.1 35.2 35.3 35.4 da Silva FB, Machado-Neto JA, Bertini V, Velloso E, Ratis CA, Calado RT, et al. Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome. J Clin Pathol 2017;70:435-42. [35]
- ↑ 36.0 36.1 36.2 36.3 36.4 36.5 36.6 36.7 36.8 Palomo L, Xicoy B, Garcia O, Mallo M, Adema V, Cabezon M, et al. Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases. Am J Hematol 2016;91:185-92.[36]
- ↑ 37.0 37.1 37.2 37.3 37.4 37.5 37.6 Gondek LP, Dunbar AJ, Szpurka H, McDevitt MA, Maciejewski JP. SNP array karyotyping allows for the detection of uniparental disomy and cryptic chromosomal abnormalities in MDS/MPD-U and MPD. PLoS One 2007;2:e1225. [37]
- ↑ 38.0 38.1 38.2 38.3 38.4 38.5 Singh NR, Morris CM, Koleth M, Wong K, Ward CM, Stevenson WS. Polyploidy in myelofibrosis: analysis by cytogenetic and SNP array indicates association with advancing disease. Mol Cytogenet 2013;6:59.[38]
- ↑ 39.00 39.01 39.02 39.03 39.04 39.05 39.06 39.07 39.08 39.09 39.10 39.11 Hahm C, Huh HJ, Mun YC, Seong CM, Chung WS, Huh J. Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression. Int J Lab Hematol 2015;37:181-9.[39]
- ↑ 40.0 40.1 Klampfl T, Harutyunyan A, Berg T, Gisslinger B, Schalling M, Bagienski K, et al. Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression. Blood 2011;118:167-76.[40]
- ↑ 41.00 41.01 41.02 41.03 41.04 41.05 41.06 41.07 41.08 41.09 41.10 41.11 41.12 41.13 Rumi E, Harutyunyan A, Elena C, Pietra D, Klampfl T, Bagienski K, et al. Identification of genomic aberrations associated with disease transformation by means of high-resolution SNP array analysis in patients with myeloproliferative neoplasm. Am J Hematol 2011;86:974-9.[41]
- ↑ 42.0 42.1 Stegelmann F, Bullinger L, Griesshammer M, Holzmann K, Habdank M, Kuhn S, et al. High-resolution single-nucleotide polymorphism array-profiling in myeloproliferative neoplasms identifies novel genomic aberrations. Haematologica 2010;95:666-9.[42]
- ↑ 43.0 43.1 43.2 Huh J, Tiu RV, Gondek LP, O'Keefe CL, Jasek M, Makishima H, et al. Characterization of chromosome arm 20q abnormalities in myeloid malignancies using genome-wide single nucleotide polymorphism array analysis. Genes Chromosomes Cancer 2010;49:390-9.[43]
- ↑ 44.0 44.1 44.2 44.3 44.4 44.5 44.6 Nowak D, Ogawa S, Muschen M, Kato M, Kawamata N, Meixel A, et al. SNP array analysis of tyrosine kinase inhibitor-resistant chronic myeloid leukemia identifies heterogeneous secondary genomic alterations. Blood 2010;115:1049-53.[44]
- ↑ 45.0 45.1 45.2 45.3 45.4 45.5 Boultwood J, Perry J, Zaman R, Fernandez-Santamaria C, Littlewood T, Kusec R, et al. High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression. Leukemia 2010;24:1139-45.[45]
- ↑ Afable MG, 2nd, Wlodarski M, Makishima H, Shaik M, Sekeres MA, Tiu RV, et al. SNP array-based karyotyping: differences and similarities between aplastic anemia and hypocellular myelodysplastic syndromes. Blood 2011;117:6876-84.[46]
- ↑ Betensky M, Babushok D, Roth JJ, Mason PJ, Biegel JA, Busse TM, et al. Clonal evolution and clinical significance of copy number neutral loss of heterozygosity of chromosome arm 6p in acquired aplastic anemia. Cancer Genet 2016;209:1-10.[47]
- ↑ Hahm C, Mun YC, Seong CM, Han SH, Chung WS, Huh J. Single nucleotide polymorphism array-based karyotyping in acute myeloid leukemia or myelodysplastic syndrome with trisomy 8 as the sole chromosomal abnormality. Acta Haematol 2013;129:154-8.[48]
- ↑ 49.0 49.1 49.2 49.3 49.4 Merkerova MD, Bystricka D, Belickova M, Krejcik Z, Zemanova Z, Polak J, et al. From cryptic chromosomal lesions to pathologically relevant genes: integration of SNP-array with gene expression profiling in myelodysplastic syndrome with normal karyotype. Genes Chromosomes Cancer 2012;51:419-28
- ↑ 50.0 50.1 Mohamedali AM, Gaken J, Ahmed M, Malik F, Smith AE, Best S, et al. High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS). Leukemia 2015;29:1928-38.[49]
- ↑ 51.0 51.1 51.2 Bajaj R, Xu F, Xiang B, Wilcox K, Diadamo AJ, Kumar R, et al. Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia. Mol Cytogenet 2011;4:3.[50]
- ↑ 52.0 52.1 Noronha TR, Rohr SS, Chauffaille Mde L. Identifying the similarities and differences between single nucleotide polymorphism array (SNPa) analysis and karyotyping in acute myeloid leukemia and myelodysplastic syndromes. Rev Bras Hematol Hemoter 2015;37:48-54. [51]
- ↑ Paulsson K, Heidenblad M, Strombeck B, Staaf J, Jonsson G, Borg A, et al. High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration. Leukemia 2006;20:840-6. [52]
- ↑ Bacher U, Haferlach T, Schnittger S, Zenger M, Meggendorfer M, Jeromin S, et al. Investigation of 305 patients with myelodysplastic syndromes and 20q deletion for associated cytogenetic and molecular genetic lesions and their prognostic impact. Br J Haematol 2014;164:822-33.[53]
- ↑ Greenberg, Peter L.; et al. (2012). "Revised international prognostic scoring system for myelodysplastic syndromes". Blood. 120 (12): 2454–2465. doi:10.1182/blood-2012-03-420489. ISSN 1528-0020. PMC 4425443. PMID 22740453.
- ↑ Schanz, Julie; et al. (2012). "New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 30 (8): 820–829. doi:10.1200/JCO.2011.35.6394. ISSN 1527-7755. PMC 4874200. PMID 22331955.
- ↑ 57.0 57.1 Bejar, Rafael; et al. (2014). "TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients". Blood. 124 (17): 2705–2712. doi:10.1182/blood-2014-06-582809. ISSN 1528-0020. PMC 4208285. PMID 25224413.
- ↑ 58.0 58.1 Traina, F.; et al. (2014). "Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms". Leukemia. 28 (1): 78–87. doi:10.1038/leu.2013.269. ISSN 1476-5551. PMID 24045501.
- ↑ 59.0 59.1 Slovak ML, Smith DD, Bedell V, Hsu YH, O'Donnell M, Forman SJ, et al. Assessing karyotype precision by microarray-based comparative genomic hybridization in the myelodysplastic/myeloproliferative syndromes. Mol Cytogenet 2010;3:23. [54]
- ↑ Mughal, Tariq I.; et al. (2015). "An International MDS/MPN Working Group's perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms". Haematologica. 100 (9): 1117–1130. doi:10.3324/haematol.2014.114660. ISSN 1592-8721. PMC 4800699. PMID 26341525.
- ↑ Puda A, Milosevic JD, Berg T, Klampfl T, Harutyunyan AS, Gisslinger B, et al. Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies. Am J Hematol 2012;87:245-50. [55]
- ↑ 62.0 62.1 Huh J, Jung CW, Kim JW, Kim HJ, Kim SH, Shin MG, et al. Genome-wide high density single-nucleotide polymorphism array-based karyotyping improves detection of clonal aberrations including der(9) deletion, but does not predict treatment outcomes after imatinib therapy in chronic myeloid leukemia. Ann Hematol 2011;90:1255-64. [56]
- ↑ Mesa, Ruben A.; et al. (2017). "NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018". Journal of the National Comprehensive Cancer Network: JNCCN. 15 (10): 1193–1207. doi:10.6004/jnccn.2017.0157. ISSN 1540-1413. PMID 28982745.