Difference between revisions of "CLL Tables: Regions of Recurrent Copy Number Change and CN-LOH"
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| − | '''Table 1 -''' '''Regions of | + | '''Table 1 -''' '''Regions of Recurrent Copy Number Change in CLL''' '''(Literature Review)'''. The is a list of clinically significant and/or recurrent CNAs selected and evaluated based on a systematic literature search performed on 72 peer-reviewed manuscripts focusing on CNAs and CN-LOH assessment in CLL published between 2000 and 2017. Table derived from Chun et al., 2018 [PMID 30554732] with permission from Cancer Genetics. |
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|'''Chromosome/''' | |'''Chromosome/''' | ||
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<nowiki>*</nowiki>Level 1: present in WHO classification or professional practice guidelines; Level 2: recurrent in well-powered studies with suspected clinical significance; Level 3: recurrent, but uncertain prognostic significance. | <nowiki>*</nowiki>Level 1: present in WHO classification or professional practice guidelines; Level 2: recurrent in well-powered studies with suspected clinical significance; Level 3: recurrent, but uncertain prognostic significance. | ||
| + | |||
| + | Abbreviations: CNA = copy number aberration; CLL = chronic lymphocytic leukemia; CN-LOH = copy-neutral loss-of-heterozygosity | ||
| + | |||
| + | |||
| + | |||
| + | '''Table 2 - Recurring regions of CN-LOH in CLL.''' Table derived from Chun et al., 2018 [PMID 30554732] with permission from Cancer Genetics. | ||
| + | {| class="wikitable" | ||
| + | |'''CN-LOH''' | ||
| + | |'''Candidate Gene''' | ||
| + | |'''Association''' | ||
| + | |'''Strength of Evidence for Prognosis (Level*)''' | ||
| + | |'''References''' | ||
| + | |- | ||
| + | |13q | ||
| + | |''miR15a/16-1'' | ||
| + | |Biallelic deletion of 13q | ||
| + | |Established (1) | ||
| + | |<ref name=":13">{{Cite journal|last=Hagenkord|first=Jill M.|last2=Monzon|first2=Federico A.|last3=Kash|first3=Shera F.|last4=Lilleberg|first4=Stan|last5=Xie|first5=Qingmei|last6=Kant|first6=Jeffrey A.|date=2010-03|title=Array-based karyotyping for prognostic assessment in chronic lymphocytic leukemia: performance comparison of Affymetrix 10K2.0, 250K Nsp, and SNP6.0 arrays|url=https://pubmed.ncbi.nlm.nih.gov/20075210|journal=The Journal of molecular diagnostics: JMD|volume=12|issue=2|pages=184–196|doi=10.2353/jmoldx.2010.090118|issn=1943-7811|pmc=2871725|pmid=20075210}}</ref> <ref>{{Cite journal|last=Pfeifer|first=Dietmar|last2=Pantic|first2=Milena|last3=Skatulla|first3=Ilona|last4=Rawluk|first4=Justyna|last5=Kreutz|first5=Clemens|last6=Martens|first6=Uwe M.|last7=Fisch|first7=Paul|last8=Timmer|first8=Jens|last9=Veelken|first9=Hendrik|date=2007-02-01|title=Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays|url=https://pubmed.ncbi.nlm.nih.gov/17053054|journal=Blood|volume=109|issue=3|pages=1202–1210|doi=10.1182/blood-2006-07-034256|issn=0006-4971|pmid=17053054}}</ref> <ref name=":14">{{Cite journal|last=Edelmann|first=Jennifer|last2=Holzmann|first2=Karlheinz|last3=Miller|first3=Florian|last4=Winkler|first4=Dirk|last5=Bühler|first5=Andreas|last6=Zenz|first6=Thorsten|last7=Bullinger|first7=Lars|last8=Kühn|first8=Michael W. M.|last9=Gerhardinger|first9=Andreas|date=2012-12-06|title=High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations|url=https://pubmed.ncbi.nlm.nih.gov/23047824|journal=Blood|volume=120|issue=24|pages=4783–4794|doi=10.1182/blood-2012-04-423517|issn=1528-0020|pmid=23047824}}</ref> <ref>{{Cite journal|last=Grygalewicz|first=Beata|last2=Woroniecka|first2=Renata|last3=Rygier|first3=Jolanta|last4=Borkowska|first4=Klaudia|last5=Rzepecka|first5=Iwona|last6=Łukasik|first6=Martyna|last7=Budziłowska|first7=Agnieszka|last8=Rymkiewicz|first8=Grzegorz|last9=Błachnio|first9=Katarzyna|date=2016|title=Monoallelic and biallelic deletions of 13q14 in a group of CLL/SLL patients investigated by CGH Haematological Cancer and SNP array (8x60K)|url=https://pubmed.ncbi.nlm.nih.gov/26740820|journal=Molecular Cytogenetics|volume=9|pages=1|doi=10.1186/s13039-015-0212-x|issn=1755-8166|pmc=4702365|pmid=26740820}}</ref> <ref>{{Cite journal|last=Gunnarsson|first=Rebeqa|last2=Mansouri|first2=Larry|last3=Isaksson|first3=Anders|last4=Göransson|first4=Hanna|last5=Cahill|first5=Nicola|last6=Jansson|first6=Mattias|last7=Rasmussen|first7=Markus|last8=Lundin|first8=Jeanette|last9=Norin|first9=Stefan|date=2011-08|title=Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/21546498|journal=Haematologica|volume=96|issue=8|pages=1161–1169|doi=10.3324/haematol.2010.039768|issn=1592-8721|pmc=3148910|pmid=21546498}}</ref> <ref name=":15">{{Cite journal|last=Parker|first=H.|last2=Rose-Zerilli|first2=M. J. J.|last3=Parker|first3=A.|last4=Chaplin|first4=T.|last5=Wade|first5=R.|last6=Gardiner|first6=A.|last7=Griffiths|first7=M.|last8=Collins|first8=A.|last9=Young|first9=B. D.|date=2011-03|title=13q deletion anatomy and disease progression in patients with chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/21151023|journal=Leukemia|volume=25|issue=3|pages=489–497|doi=10.1038/leu.2010.288|issn=1476-5551|pmid=21151023}}</ref> <ref>{{Cite journal|last=Lehmann|first=Sören|last2=Ogawa|first2=Seishi|last3=Raynaud|first3=Sophie D.|last4=Sanada|first4=Masashi|last5=Nannya|first5=Yasuhito|last6=Ticchioni|first6=Michel|last7=Bastard|first7=Christian|last8=Kawamata|first8=Norihiko|last9=Koeffler|first9=H. Phillip|date=2008-03-15|title=Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/18246537|journal=Cancer|volume=112|issue=6|pages=1296–1305|doi=10.1002/cncr.23270|issn=0008-543X|pmid=18246537}}</ref> <ref>{{Cite journal|last=Ouillette|first=Peter|last2=Collins|first2=Roxane|last3=Shakhan|first3=Sajid|last4=Li|first4=Jinghui|last5=Li|first5=Cheng|last6=Shedden|first6=Kerby|last7=Malek|first7=Sami N.|date=2011-11-01|title=The prognostic significance of various 13q14 deletions in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/21890456|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=17|issue=21|pages=6778–6790|doi=10.1158/1078-0432.CCR-11-0785|issn=1078-0432|pmc=3207001|pmid=21890456}}</ref> | ||
| + | |- | ||
| + | |17p13 | ||
| + | |''[[TP53]]'' | ||
| + | |Homozygous ''TP53'' mutations | ||
| + | |Established (1) | ||
| + | |<ref name=":13" /> <ref name=":14" /> <ref name=":16">{{Cite journal|last=Stevens-Kroef|first=Marian Jpl|last2=van den Berg|first2=Eva|last3=Olde Weghuis|first3=Daniel|last4=Geurts van Kessel|first4=Ad|last5=Pfundt|first5=Rolph|last6=Linssen-Wiersma|first6=Matty|last7=Benjamins|first7=Marloes|last8=Dijkhuizen|first8=Trijnie|last9=Groenen|first9=Patricia Jta|date=2014-01-09|title=Identification of prognostic relevant chromosomal abnormalities in chronic lymphocytic leukemia using microarray-based genomic profiling|url=https://pubmed.ncbi.nlm.nih.gov/24401281|journal=Molecular Cytogenetics|volume=7|issue=1|pages=3|doi=10.1186/1755-8166-7-3|issn=1755-8166|pmc=3905918|pmid=24401281}}</ref> <ref name=":15" /> <ref>{{Cite journal|last=Saddler|first=Chris|last2=Ouillette|first2=Peter|last3=Kujawski|first3=Lisa|last4=Shangary|first4=Sanjeev|last5=Talpaz|first5=Moshe|last6=Kaminski|first6=Mark|last7=Erba|first7=Harry|last8=Shedden|first8=Kerby|last9=Wang|first9=Shaomeng|date=2008-02-01|title=Comprehensive biomarker and genomic analysis identifies p53 status as the major determinant of response to MDM2 inhibitors in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/17971485|journal=Blood|volume=111|issue=3|pages=1584–1593|doi=10.1182/blood-2007-09-112698|issn=0006-4971|pmid=17971485}}</ref> | ||
| + | |- | ||
| + | |11q13-qter | ||
| + | |Includes ''[[ATM]]'' | ||
| + | |Monoallelic ''ATM'' deletion | ||
| + | |Suspected (2) | ||
| + | |<ref name=":14" /> <ref name=":15" /> | ||
| + | |- | ||
| + | |20q11 | ||
| + | |Unknown | ||
| + | |None | ||
| + | |N/A (3) | ||
| + | |<ref name=":16" /> <ref>{{Cite journal|last=Pei|first=Jianming|last2=Robu|first2=Valentin|last3=Feder|first3=Madelyn|last4=Cheung|first4=Mitchell|last5=Neumann-Domer|first5=Erin|last6=Talarchek|first6=Jacqueline|last7=Dulaimi|first7=Essel|last8=Millenson|first8=Michael M.|last9=Testa|first9=Joseph R.|date=2014-03|title=Copy neutral loss of heterozygosity in 20q in chronic lymphocytic leukemia/small lymphocytic lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/24704113|journal=Cancer Genetics|volume=207|issue=3|pages=98–102|doi=10.1016/j.cancergen.2014.02.005|issn=2210-7762|pmc=4010307|pmid=24704113}}</ref> | ||
| + | |- | ||
| + | |1p36 | ||
| + | |Unknown | ||
| + | |None | ||
| + | |N/A (3) | ||
| + | |<ref name=":14" /> <ref>{{Cite journal|last=Xu|first=Xinjie|last2=Johnson|first2=Eric B.|last3=Leverton|first3=Lisa|last4=Arthur|first4=Ashley|last5=Watson|first5=Quinn|last6=Chang|first6=Faye L.|last7=Raca|first7=Gordana|last8=Laffin|first8=Jennifer J.|date=2013-09|title=The advantage of using SNP array in clinical testing for hematological malignancies--a comparative study of three genetic testing methods|url=https://pubmed.ncbi.nlm.nih.gov/24269304|journal=Cancer Genetics|volume=206|issue=9-10|pages=317–326|doi=10.1016/j.cancergen.2013.09.001|issn=2210-7762|pmid=24269304}}</ref> | ||
| + | |} | ||
| + | <nowiki>*</nowiki>Level 1: present in WHO classification or professional practice guidelines; Level 2: recurrent in well-powered studies with suspected clinical significance; Level 3: recurrent, but uncertain prognostic significance | ||
| + | |||
| + | |||
| + | |||
| + | '''Table 3 - Recurrent mutated genes in CLL.''' Table derived from Chun et al., 2018 [PMID 30554732] with permission from Cancer Genetics. | ||
| + | {| class="wikitable" | ||
| + | |'''Gene''' | ||
| + | |'''Locus''' | ||
| + | |'''Function''' | ||
| + | |'''Mutation Type''' | ||
| + | |'''Prevalence (%)''' | ||
| + | |'''Prognostic Significance''' | ||
| + | |'''Strength of Evidence (Level*)''' | ||
| + | |'''Comments''' | ||
| + | |'''References''' | ||
| + | |- | ||
| + | |''[[ATM]]'' | ||
| + | |11q22.3 | ||
| + | |DNA repair and cell-cycle control | ||
| + | |Missense, nonsense, indel | ||
| + | |10-14 | ||
| + | |Unfavorable | ||
| + | |Established (1) | ||
| + | |Associated with unmut''IGHV'' and 11q-; Candidate driver gene | ||
| + | |<ref name=":17">{{Cite journal|last=Wierda|first=William G.|last2=Zelenetz|first2=Andrew D.|last3=Gordon|first3=Leo I.|last4=Abramson|first4=Jeremy S.|last5=Advani|first5=Ranjana H.|last6=Andreadis|first6=C. Babis|last7=Bartlett|first7=Nancy|last8=Byrd|first8=John C.|last9=Caimi|first9=Paolo|date=03 2017|title=NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 1.2017|url=https://pubmed.ncbi.nlm.nih.gov/28275031|journal=Journal of the National Comprehensive Cancer Network: JNCCN|volume=15|issue=3|pages=293–311|doi=10.6004/jnccn.2017.0030|issn=1540-1413|pmid=28275031}}</ref> <ref name=":18">{{Cite journal|last=Campregher|first=Paulo Vidal|last2=Hamerschlak|first2=Nelson|date=2014-08|title=Novel prognostic gene mutations identified in chronic lymphocytic leukemia and their impact on clinical practice|url=https://pubmed.ncbi.nlm.nih.gov/24548608|journal=Clinical Lymphoma, Myeloma & Leukemia|volume=14|issue=4|pages=271–276|doi=10.1016/j.clml.2013.12.016|issn=2152-2669|pmid=24548608}}</ref> | ||
| + | |- | ||
| + | |''[[BIRC3]]'' | ||
| + | |11q22.2 | ||
| + | |Apoptosis inhibitor | ||
| + | |Frameshift, nonsense, whole gene deletion | ||
| + | |1-10 | ||
| + | |||
| + | (higher in previously treated patients) | ||
| + | |Unfavorable | ||
| + | |Established (1) | ||
| + | |In ~25% of fludarabine-refractory CLL; Candidate driver gene | ||
| + | |<ref name=":19">{{Cite journal|last=Strefford|first=Jonathan C.|date=2015-04|title=The genomic landscape of chronic lymphocytic leukaemia: biological and clinical implications|url=https://pubmed.ncbi.nlm.nih.gov/25496136|journal=British Journal of Haematology|volume=169|issue=1|pages=14–31|doi=10.1111/bjh.13254|issn=1365-2141|pmid=25496136}}</ref> <ref>{{Cite journal|last=Alsolami|first=Reem|last2=Knight|first2=Samantha Jl|last3=Schuh|first3=Anna|date=2013-06-01|title=Clinical application of targeted and genome-wide technologies: can we predict treatment responses in chronic lymphocytic leukemia?|url=https://pubmed.ncbi.nlm.nih.gov/24611071|journal=Personalized Medicine|volume=10|issue=4|pages=361–376|doi=10.2217/pme.13.33|issn=1741-0541|pmc=3943176|pmid=24611071}}</ref> <ref name=":20">{{Cite journal|last=Baliakas|first=P.|last2=Hadzidimitriou|first2=A.|last3=Sutton|first3=L.-A.|last4=Rossi|first4=D.|last5=Minga|first5=E.|last6=Villamor|first6=N.|last7=Larrayoz|first7=M.|last8=Kminkova|first8=J.|last9=Agathangelidis|first9=A.|date=2015-02|title=Recurrent mutations refine prognosis in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/24943832|journal=Leukemia|volume=29|issue=2|pages=329–336|doi=10.1038/leu.2014.196|issn=1476-5551|pmid=24943832}}</ref> <ref name=":21">{{Cite journal|last=Rossi|first=Davide|last2=Rasi|first2=Silvia|last3=Spina|first3=Valeria|last4=Bruscaggin|first4=Alessio|last5=Monti|first5=Sara|last6=Ciardullo|first6=Carmela|last7=Deambrogi|first7=Clara|last8=Khiabanian|first8=Hossein|last9=Serra|first9=Roberto|date=2013-02-21|title=Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/23243274|journal=Blood|volume=121|issue=8|pages=1403–1412|doi=10.1182/blood-2012-09-458265|issn=1528-0020|pmc=3578955|pmid=23243274}}</ref> | ||
| + | |- | ||
| + | |''[[CHD2]]'' | ||
| + | |15q26.1 | ||
| + | |Chromatin remodeler | ||
| + | |Missense, truncation | ||
| + | |5-10 | ||
| + | |Unknown | ||
| + | |N/A (3) | ||
| + | | | ||
| + | |<ref name=":19" /> <ref>{{Cite journal|last=Rodríguez|first=David|last2=Bretones|first2=Gabriel|last3=Quesada|first3=Víctor|last4=Villamor|first4=Neus|last5=Arango|first5=Javier R.|last6=López-Guillermo|first6=Armando|last7=Ramsay|first7=Andrew J.|last8=Baumann|first8=Tycho|last9=Quirós|first9=Pedro M.|date=2015-07-09|title=Mutations in CHD2 cause defective association with active chromatin in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/26031915|journal=Blood|volume=126|issue=2|pages=195–202|doi=10.1182/blood-2014-10-604959|issn=1528-0020|pmid=26031915}}</ref> | ||
| + | |- | ||
| + | |''[[FBXW7]]'' | ||
| + | |4q31.3 | ||
| + | |Ubiquitin ligase subunit/targets include ''[[NOTCH1]]'' | ||
| + | |Missense | ||
| + | |4 | ||
| + | |Unknown | ||
| + | |N/A (3) | ||
| + | |Exclusive to ''[[NOTCH1]]'' mutation patients; Negatively regulates ''[[NOTCH1]]'' | ||
| + | |<ref>{{Cite journal|last=Wang|first=Lili|last2=Lawrence|first2=Michael S.|last3=Wan|first3=Youzhong|last4=Stojanov|first4=Petar|last5=Sougnez|first5=Carrie|last6=Stevenson|first6=Kristen|last7=Werner|first7=Lillian|last8=Sivachenko|first8=Andrey|last9=DeLuca|first9=David S.|date=2011-12-29|title=SF3B1 and other novel cancer genes in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22150006|journal=The New England Journal of Medicine|volume=365|issue=26|pages=2497–2506|doi=10.1056/NEJMoa1109016|issn=1533-4406|pmc=3685413|pmid=22150006}}</ref> | ||
| + | |- | ||
| + | |''[[MYD88]]'' | ||
| + | |3p22.2 | ||
| + | |Inflammatory pathway signal transducer | ||
| + | |Missense | ||
| + | |2-10 | ||
| + | |Favorable/ | ||
| + | |||
| + | No effect | ||
| + | |Suspected (2) | ||
| + | |Candidate driver gene | ||
| + | |<ref name=":20" /> <ref name=":21" /> <ref name=":22">{{Cite journal|last=Filip|first=Agata A.|date=2013-09|title=New boys in town: prognostic role of SF3B1, NOTCH1 and other cryptic alterations in chronic lymphocytic leukemia and how it works|url=https://pubmed.ncbi.nlm.nih.gov/23343182|journal=Leukemia & Lymphoma|volume=54|issue=9|pages=1876–1881|doi=10.3109/10428194.2013.769049|issn=1029-2403|pmid=23343182}}</ref> | ||
| + | |- | ||
| + | |''[[NOTCH1]]'' | ||
| + | |9q34.3 | ||
| + | |Intercellular signaling | ||
| + | |Missense, nonsense, insertion, duplication, frameshift | ||
| + | |4-10 | ||
| + | |||
| + | (diagnosis) | ||
| + | |||
| + | 12-30 | ||
| + | |||
| + | (progression) | ||
| + | |Unfavorable | ||
| + | |Established (1) | ||
| + | |Associated with +12; Candidate driver gene | ||
| + | |<ref>{{Cite journal|last=Nabhan|first=Chadi|last2=Raca|first2=Gordana|last3=Wang|first3=Y. Lynn|date=2015-10|title=Predicting Prognosis in Chronic Lymphocytic Leukemia in the Contemporary Era|url=https://pubmed.ncbi.nlm.nih.gov/26181643|journal=JAMA oncology|volume=1|issue=7|pages=965–974|doi=10.1001/jamaoncol.2015.0779|issn=2374-2445|pmid=26181643}}</ref> <ref name=":18" /> <ref name=":21" /> <ref>{{Cite journal|last=Balatti|first=Veronica|last2=Bottoni|first2=Arianna|last3=Palamarchuk|first3=Alexey|last4=Alder|first4=Hansjuerg|last5=Rassenti|first5=Laura Z.|last6=Kipps|first6=Thomas J.|last7=Pekarsky|first7=Yuri|last8=Croce|first8=Carlo M.|date=2012-01-12|title=NOTCH1 mutations in CLL associated with trisomy 12|url=https://pubmed.ncbi.nlm.nih.gov/22086416|journal=Blood|volume=119|issue=2|pages=329–331|doi=10.1182/blood-2011-10-386144|issn=1528-0020|pmc=3257004|pmid=22086416}}</ref> <ref>{{Cite journal|last=Del Giudice|first=Ilaria|last2=Rossi|first2=Davide|last3=Chiaretti|first3=Sabina|last4=Marinelli|first4=Marilisa|last5=Tavolaro|first5=Simona|last6=Gabrielli|first6=Sara|last7=Laurenti|first7=Luca|last8=Marasca|first8=Roberto|last9=Rasi|first9=Silvia|date=2012-03|title=NOTCH1 mutations in +12 chronic lymphocytic leukemia (CLL) confer an unfavorable prognosis, induce a distinctive transcriptional profiling and refine the intermediate prognosis of +12 CLL|url=https://pubmed.ncbi.nlm.nih.gov/22207691|journal=Haematologica|volume=97|issue=3|pages=437–441|doi=10.3324/haematol.2011.060129|issn=1592-8721|pmc=3291600|pmid=22207691}}</ref> | ||
| + | |- | ||
| + | |''[[POT1]]'' | ||
| + | |7q31.33 | ||
| + | |Telomere protector/ | ||
| + | |||
| + | stabilizer; component of telomerase RNP complex | ||
| + | |Missense, frameshift, splicing | ||
| + | |5-10 | ||
| + | |Unfavorable | ||
| + | |Suspected (2) | ||
| + | |Associated with familial CLL | ||
| + | |<ref>{{Cite journal|last=Herling|first=Carmen Diana|last2=Klaumünzer|first2=Marion|last3=Rocha|first3=Cristiano Krings|last4=Altmüller|first4=Janine|last5=Thiele|first5=Holger|last6=Bahlo|first6=Jasmin|last7=Kluth|first7=Sandra|last8=Crispatzu|first8=Giuliano|last9=Herling|first9=Marco|date=07 21, 2016|title=Complex karyotypes and KRAS and POT1 mutations impact outcome in CLL after chlorambucil-based chemotherapy or chemoimmunotherapy|url=https://pubmed.ncbi.nlm.nih.gov/27226433|journal=Blood|volume=128|issue=3|pages=395–404|doi=10.1182/blood-2016-01-691550|issn=1528-0020|pmid=27226433}}</ref> <ref>{{Cite journal|last=Ramsay|first=Andrew J.|last2=Quesada|first2=Víctor|last3=Foronda|first3=Miguel|last4=Conde|first4=Laura|last5=Martínez-Trillos|first5=Alejandra|last6=Villamor|first6=Neus|last7=Rodríguez|first7=David|last8=Kwarciak|first8=Agnieszka|last9=Garabaya|first9=Cecilia|date=2013-05|title=POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/23502782|journal=Nature Genetics|volume=45|issue=5|pages=526–530|doi=10.1038/ng.2584|issn=1546-1718|pmid=23502782}}</ref> <ref>{{Cite journal|last=Speedy|first=Helen E.|last2=Kinnersley|first2=Ben|last3=Chubb|first3=Daniel|last4=Broderick|first4=Peter|last5=Law|first5=Philip J.|last6=Litchfield|first6=Kevin|last7=Jayne|first7=Sandrine|last8=Dyer|first8=Martin J. S.|last9=Dearden|first9=Claire|date=11 10, 2016|title=Germ line mutations in shelterin complex genes are associated with familial chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/27528712|journal=Blood|volume=128|issue=19|pages=2319–2326|doi=10.1182/blood-2016-01-695692|issn=1528-0020|pmc=5271173|pmid=27528712}}</ref> | ||
| + | |- | ||
| + | |''[[SF3B1]]'' | ||
| + | |2q33.1 | ||
| + | |Spliceosome component | ||
| + | |Missense | ||
| + | |10 -18 | ||
| + | |Unfavorable | ||
| + | |Established (1) | ||
| + | |Enriched in patients with del(11q) and unmut''IGHV''; Candidate driver gene for disease progression | ||
| + | |<ref name=":20" /> <ref name=":21" /> <ref>{{Cite journal|last=Mitsui|first=Takeki|last2=Koiso|first2=Hiromi|last3=Nakahashi|first3=Hirotaka|last4=Saitoh|first4=Akio|last5=Shimizu|first5=Hiroaki|last6=Ishizaki|first6=Takuma|last7=Ogawa|first7=Yoshiyuki|last8=Takizawa|first8=Makiko|last9=Yokohama|first9=Akihiko|date=2016-02|title=SF3B1 and IGHV gene mutation status predict poor prognosis in Japanese CLL patients|url=https://pubmed.ncbi.nlm.nih.gov/26588928|journal=International Journal of Hematology|volume=103|issue=2|pages=219–226|doi=10.1007/s12185-015-1912-z|issn=1865-3774|pmid=26588928}}</ref> <ref>{{Cite journal|last=Quesada|first=Víctor|last2=Conde|first2=Laura|last3=Villamor|first3=Neus|last4=Ordóñez|first4=Gonzalo R.|last5=Jares|first5=Pedro|last6=Bassaganyas|first6=Laia|last7=Ramsay|first7=Andrew J.|last8=Beà|first8=Sílvia|last9=Pinyol|first9=Magda|date=2011-12-11|title=Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22158541|journal=Nature Genetics|volume=44|issue=1|pages=47–52|doi=10.1038/ng.1032|issn=1546-1718|pmid=22158541}}</ref> <ref>{{Cite journal|last=Wan|first=Youzhong|last2=Wu|first2=Catherine J.|date=2013-06-06|title=SF3B1 mutations in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/23568491|journal=Blood|volume=121|issue=23|pages=4627–4634|doi=10.1182/blood-2013-02-427641|issn=1528-0020|pmc=3674664|pmid=23568491}}</ref> | ||
| + | |- | ||
| + | |''[[TP53]]'' | ||
| + | |17p13.1 | ||
| + | |DNA repair and cell-cycle control | ||
| + | |Missense | ||
| + | |5-10 | ||
| + | |||
| + | (higher with progressive disease) | ||
| + | |Unfavorable | ||
| + | |Established (1) | ||
| + | | | ||
| + | |<ref name=":17" /> <ref name=":19" /> <ref>{{Cite journal|last=Rossi|first=Davide|last2=Khiabanian|first2=Hossein|last3=Spina|first3=Valeria|last4=Ciardullo|first4=Carmela|last5=Bruscaggin|first5=Alessio|last6=Famà|first6=Rosella|last7=Rasi|first7=Silvia|last8=Monti|first8=Sara|last9=Deambrogi|first9=Clara|date=2014-04-03|title=Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/24501221|journal=Blood|volume=123|issue=14|pages=2139–2147|doi=10.1182/blood-2013-11-539726|issn=1528-0020|pmc=4017291|pmid=24501221}}</ref> <ref>{{Cite journal|last=Zenz|first=Thorsten|last2=Eichhorst|first2=Barbara|last3=Busch|first3=Raymonde|last4=Denzel|first4=Tina|last5=Häbe|first5=Sonja|last6=Winkler|first6=Dirk|last7=Bühler|first7=Andreas|last8=Edelmann|first8=Jennifer|last9=Bergmann|first9=Manuela|date=2010-10-10|title=TP53 mutation and survival in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/20697090|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=28|issue=29|pages=4473–4479|doi=10.1200/JCO.2009.27.8762|issn=1527-7755|pmid=20697090}}</ref> <ref>{{Cite journal|last=Stilgenbauer|first=Stephan|last2=Schnaiter|first2=Andrea|last3=Paschka|first3=Peter|last4=Zenz|first4=Thorsten|last5=Rossi|first5=Marianna|last6=Döhner|first6=Konstanze|last7=Bühler|first7=Andreas|last8=Böttcher|first8=Sebastian|last9=Ritgen|first9=Matthias|date=2014-05-22|title=Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial|url=https://pubmed.ncbi.nlm.nih.gov/24652989|journal=Blood|volume=123|issue=21|pages=3247–3254|doi=10.1182/blood-2014-01-546150|issn=1528-0020|pmid=24652989}}</ref> | ||
| + | |- | ||
| + | |''[[XPO1]]'' | ||
| + | |2p15 | ||
| + | |Exports proteins/RNA fragments from nucleus into cytoplasm | ||
| + | |Missense | ||
| + | |5-7.5 | ||
| + | |Unfavorable/ | ||
| + | |||
| + | high risk of progression | ||
| + | |Suspected (2) | ||
| + | |Associated with unmut''IGHV'' | ||
| + | |<ref>{{Cite journal|last=Cosson|first=A.|last2=Chapiro|first2=E.|last3=Bougacha|first3=N.|last4=Lambert|first4=J.|last5=Herbi|first5=L.|last6=Cung|first6=H.-A.|last7=Algrin|first7=C.|last8=Keren|first8=B.|last9=Damm|first9=F.|date=07 2017|title=Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1|url=https://pubmed.ncbi.nlm.nih.gov/28344316|journal=Leukemia|volume=31|issue=7|pages=1625–1629|doi=10.1038/leu.2017.100|issn=1476-5551|pmid=28344316}}</ref> <ref name=":22" /> <ref>{{Cite journal|last=Jain|first=Nitin|last2=O'Brien|first2=Susan|date=2015-07-23|title=Initial treatment of CLL: integrating biology and functional status|url=https://pubmed.ncbi.nlm.nih.gov/26065656|journal=Blood|volume=126|issue=4|pages=463–470|doi=10.1182/blood-2015-04-585067|issn=1528-0020|pmc=4624441|pmid=26065656}}</ref> | ||
| + | |} | ||
| + | <nowiki>*</nowiki>Level 1: present in WHO classification or professional practice guidelines; Level 2: recurrent in well-powered studies with suspected clinical significance; Level 3: recurrent, but uncertain prognostic significance | ||
| + | |||
==Reference== | ==Reference== | ||
<references /> | <references /> | ||
Latest revision as of 22:25, 7 November 2020
Table 1 - Regions of Recurrent Copy Number Change in CLL (Literature Review). The is a list of clinically significant and/or recurrent CNAs selected and evaluated based on a systematic literature search performed on 72 peer-reviewed manuscripts focusing on CNAs and CN-LOH assessment in CLL published between 2000 and 2017. Table derived from Chun et al., 2018 [PMID 30554732] with permission from Cancer Genetics.
| Chromosome/
Region |
Abnormality Type | Prevalence (%) | Relevant Genes | Strength of Evidence for Gene | Prognostic Significance | Strength of Evidence for Prognosis (Level*) | Comments | References |
| 1p | Gain | ?2-5 | Unknown | N/A | Favorable | Suspected (2) | [1] [2] [3] | |
| 1q23.2q23.3 | Loss | 15 | Unknown | N/A | Unknown | N/A (3) | [4] [5] [6] | |
| 2p12p25.3 | Gain | 5-30 | ACP1, MYCN, ALK, REL, BCL11A | MYCN (Established), REL, BCL11A (Candidate) | Unfavorable | Established (if MYCN included) (1) | [1] [2] [3] [4] [5] [7] [8] [9] [10] [11] [12] [13] | |
| 3p21.31 | Loss | 1-5 | ATRIP, CDC25A | Candidate | Unknown | N/A (3) | [4] [14] [15] | |
| 3q | Gain | 2-19 | Unknown | N/A | Unfavorable | Suspected (2) | Appears to be particularly prevalent in Japanese | [2] [16] [17] |
| 4p15.2p16.3 | Loss | 14 | Unknown | N/A | Unfavorable (occurred with del(11q) or del(17p)) | Suspected (2) | [18] | |
| 6p25.3 | Gain | 1 | Unknown | N/A | Unknown | N/A (3) | [4] | |
| 6p22.1 | Loss | 1 | Histone cluster, HFE | Candidate | Unknown | N/A (3) | [4] | |
| 6q | Loss | 3-6 | FOXO3 | Candidate | Intermediate | Suspected (2) | [19] [20] [21] [22] | |
| 7p | Gain | 5-6 | Unknown | N/A | Intermediate | Suspected (2) | [2] | |
| 7q | Loss | 1-2 | Unknown | N/A | Unknown | N/A (3) | [2] [10] | |
| 8p21 | Loss | 2-5 | TRIM35 | Candidate | Unfavorable | Suspected (2) | Associated with established unfavorable changes (11q- and 17p-). Not established as an independent prognosticator | [2] [23] |
| 8q24.1 | Gain | 5 | MYC | Candidate | Unfavorable | Suspected (2) | Often associated with 11q and 17p deletion; may not be independent [2] | [2] [4] |
| 9q13q21.11 | Loss | 1 | Unknown | N/A | Unknown | N/A (3) | [4] | |
| 10q24 | Loss | 2 | Unknown | N/A | Unknown | N/A (3) | Clustered around NFKB2 gene locus | [4] [9] [24] |
| 11q22.3 | Loss | 10-20 | ATM, BIRC3, MRE11, H2AFX | ATM established, Others Candidate | Unfavorable | Established (1) | [25] | |
| 12 | Gain | 10-20 | Unknown | N/A | Intermediate | Established (1) | Unfavorable if NOTCH1 mutation is present | [25] |
| 13q14 | Loss | 50-60 | DLEU2, MIR15A, MIR16-1, DLEU1 | Established | Favorable | Established (1) | Co-deletion of RB1 may negatively impact time to treatment | [25] [26] [27] |
| 14q24.1q32.3 | Loss | 2 | Unknown | N/A | Unknown | N/A (3) | Associated with trisomy 12 | [4] [28] [29] |
| 15q15.1 | Loss | 4 | MGA | Candidate | Unknown | N/A (3) | [4] [9] | |
| 17p13.1 | Loss | 5-15 | TP53 | Established | Unfavorable | Established (1) | [25] | |
| 17q | Gain | 1 | Unknown | N/A | Unfavorable | Suspected (2) | [2] | |
| 18p | Loss | 3 | Unknown | N/A | Unfavorable | Suspected (2) | [2] [4] | |
| 18 | Gain | 4 | Unknown | N/A | Unfavorable | Established (1) | Associated with trisomy 12 | [30] |
| 19 | Gain | 2-5 | Unknown | N/A | Unfavorable | Established (1) | Associated with trisomy 12 | [4] [9] [18] [24] [30] |
| Genomic complexity | 3 or more CNAs | 10-15 | N/A | Unfavorable | Established (1) | [9] [10] [14] [31] | ||
| Chromothripsis | (>10 copy number states of 2 and 3) | 5 | SETD2, other markers across genome not defined | Established | Unfavorable | Established (1) | [4] [27] [32] |
*Level 1: present in WHO classification or professional practice guidelines; Level 2: recurrent in well-powered studies with suspected clinical significance; Level 3: recurrent, but uncertain prognostic significance.
Abbreviations: CNA = copy number aberration; CLL = chronic lymphocytic leukemia; CN-LOH = copy-neutral loss-of-heterozygosity
Table 2 - Recurring regions of CN-LOH in CLL. Table derived from Chun et al., 2018 [PMID 30554732] with permission from Cancer Genetics.
| CN-LOH | Candidate Gene | Association | Strength of Evidence for Prognosis (Level*) | References |
| 13q | miR15a/16-1 | Biallelic deletion of 13q | Established (1) | [33] [34] [35] [36] [37] [38] [39] [40] |
| 17p13 | TP53 | Homozygous TP53 mutations | Established (1) | [33] [35] [41] [38] [42] |
| 11q13-qter | Includes ATM | Monoallelic ATM deletion | Suspected (2) | [35] [38] |
| 20q11 | Unknown | None | N/A (3) | [41] [43] |
| 1p36 | Unknown | None | N/A (3) | [35] [44] |
*Level 1: present in WHO classification or professional practice guidelines; Level 2: recurrent in well-powered studies with suspected clinical significance; Level 3: recurrent, but uncertain prognostic significance
Table 3 - Recurrent mutated genes in CLL. Table derived from Chun et al., 2018 [PMID 30554732] with permission from Cancer Genetics.
| Gene | Locus | Function | Mutation Type | Prevalence (%) | Prognostic Significance | Strength of Evidence (Level*) | Comments | References |
| ATM | 11q22.3 | DNA repair and cell-cycle control | Missense, nonsense, indel | 10-14 | Unfavorable | Established (1) | Associated with unmutIGHV and 11q-; Candidate driver gene | [45] [46] |
| BIRC3 | 11q22.2 | Apoptosis inhibitor | Frameshift, nonsense, whole gene deletion | 1-10
(higher in previously treated patients) |
Unfavorable | Established (1) | In ~25% of fludarabine-refractory CLL; Candidate driver gene | [47] [48] [49] [50] |
| CHD2 | 15q26.1 | Chromatin remodeler | Missense, truncation | 5-10 | Unknown | N/A (3) | [47] [51] | |
| FBXW7 | 4q31.3 | Ubiquitin ligase subunit/targets include NOTCH1 | Missense | 4 | Unknown | N/A (3) | Exclusive to NOTCH1 mutation patients; Negatively regulates NOTCH1 | [52] |
| MYD88 | 3p22.2 | Inflammatory pathway signal transducer | Missense | 2-10 | Favorable/
No effect |
Suspected (2) | Candidate driver gene | [49] [50] [53] |
| NOTCH1 | 9q34.3 | Intercellular signaling | Missense, nonsense, insertion, duplication, frameshift | 4-10
(diagnosis) 12-30 (progression) |
Unfavorable | Established (1) | Associated with +12; Candidate driver gene | [54] [46] [50] [55] [56] |
| POT1 | 7q31.33 | Telomere protector/
stabilizer; component of telomerase RNP complex |
Missense, frameshift, splicing | 5-10 | Unfavorable | Suspected (2) | Associated with familial CLL | [57] [58] [59] |
| SF3B1 | 2q33.1 | Spliceosome component | Missense | 10 -18 | Unfavorable | Established (1) | Enriched in patients with del(11q) and unmutIGHV; Candidate driver gene for disease progression | [49] [50] [60] [61] [62] |
| TP53 | 17p13.1 | DNA repair and cell-cycle control | Missense | 5-10
(higher with progressive disease) |
Unfavorable | Established (1) | [45] [47] [63] [64] [65] | |
| XPO1 | 2p15 | Exports proteins/RNA fragments from nucleus into cytoplasm | Missense | 5-7.5 | Unfavorable/
high risk of progression |
Suspected (2) | Associated with unmutIGHV | [66] [53] [67] |
*Level 1: present in WHO classification or professional practice guidelines; Level 2: recurrent in well-powered studies with suspected clinical significance; Level 3: recurrent, but uncertain prognostic significance
Reference
- ↑ 1.0 1.1 D, Pfeifer; et al. (2007). "Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays". PMID 17053054.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 J, Houldsworth; et al. (2014). "Genomic imbalance defines three prognostic groups for risk stratification of patients with chronic lymphocytic leukemia". doi:10.3109/10428194.2013.845882. PMC 6905429. PMID 24047479.CS1 maint: PMC format (link)
- ↑ 3.0 3.1 E, Chapiro; et al. (2010). "Gain of the short arm of chromosome 2 (2p) is a frequent recurring chromosome aberration in untreated chronic lymphocytic leukemia (CLL) at advanced stages". PMID 19406473.
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 J, Edelmann; et al. (2012). "High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations". PMID 23047824.
- ↑ 5.0 5.1 D, Ma; et al. (2011). "Array comparative genomic hybridization analysis identifies recurrent gain of chromosome 2p25.3 involving the ACP1 and MYCN genes in chronic lymphocytic leukemia". doi:10.1016/j.clml.2011.03.031. PMC 4845643. PMID 22035742.CS1 maint: PMC format (link)
- ↑ A, Tyybakinoja; et al. (2007). "High-resolution oligonucleotide array-CGH pinpoints genes involved in cryptic losses in chronic lymphocytic leukemia". PMID 17901694.
- ↑ L, Shao; et al. (2010). "Array comparative genomic hybridization detects chromosomal abnormalities in hematological cancers that are not detected by conventional cytogenetics". doi:10.2353/jmoldx.2010.090192. PMC 2928432. PMID 20724749.CS1 maint: PMC format (link)
- ↑ A, Patel; et al. (2008). "Validation of a targeted DNA microarray for the clinical evaluation of recurrent abnormalities in chronic lymphocytic leukemia". PMID 18161787.
- ↑ 9.0 9.1 9.2 9.3 9.4 Mj, Stevens-Kroef; et al. (2014). "Identification of prognostic relevant chromosomal abnormalities in chronic lymphocytic leukemia using microarray-based genomic profiling". doi:10.1186/1755-8166-7-3. PMC 3905918. PMID 24401281.CS1 maint: PMC format (link)
- ↑ 10.0 10.1 10.2 Cd, Schweighofer; et al. (2013). "Genomic variation by whole-genome SNP mapping arrays predicts time-to-event outcome in patients with chronic lymphocytic leukemia: a comparison of CLL and HapMap genotypes". doi:10.1016/j.jmoldx.2012.09.006. PMC 3586684. PMID 23273604.CS1 maint: PMC format (link)
- ↑ S, Fabris; et al. (2013). "Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia". PMID 23044996.
- ↑ F, Forconi; et al. (2008). "Genome-wide DNA analysis identifies recurrent imbalances predicting outcome in chronic lymphocytic leukaemia with 17p deletion". PMID 18752589.
- ↑ M, Jarosova; et al. (2010). "Gain of chromosome 2p in chronic lymphocytic leukemia: significant heterogeneity and a new recurrent dicentric rearrangement". PMID 20078324.
- ↑ 14.0 14.1 Ka, Kolquist; et al. (2011). "Evaluation of chronic lymphocytic leukemia by oligonucleotide-based microarray analysis uncovers novel aberrations not detected by FISH or cytogenetic analysis". doi:10.1186/1755-8166-4-25. PMC 3253687. PMID 22087757.CS1 maint: PMC format (link)
- ↑ I, Salaverria; et al. (2015). "Detection of chromothripsis-like patterns with a custom array platform for chronic lymphocytic leukemia". doi:10.1002/gcc.22277. PMC 4832286. PMID 26305789.CS1 maint: PMC format (link)
- ↑ N, Kawamata; et al. (2013). "Genetic differences between Asian and Caucasian chronic lymphocytic leukemia". doi:10.3892/ijo.2013.1966. PMC 3775563. PMID 23708256.CS1 maint: PMC format (link)
- ↑ K, Tsukasaki; et al. (2006). "Comparative genomic hybridization analysis of Japanese B-cell chronic lymphocytic leukemia: correlation with clinical course". PMID 16321855.
- ↑ 18.0 18.1 R, Gunnarsson; et al. (2011). "Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia". doi:10.3324/haematol.2010.039768. PMC 3148910. PMID 21546498.CS1 maint: PMC format (link)
- ↑ A, Cuneo; et al. (2004). "Chronic lymphocytic leukemia with 6q- shows distinct hematological features and intermediate prognosis". PMID 14712287.
- ↑ Dm, Wang; et al. (2011). "Intermediate prognosis of 6q deletion in chronic lymphocytic leukemia". PMID 21281237.
- ↑ M, Jarosova; et al. (2017). "Chromosome 6q deletion correlates with poor prognosis and low relative expression of FOXO3 in chronic lymphocytic leukemia patients". PMID 28699185.
- ↑ C, Nabhan; et al. (2015). "Predicting Prognosis in Chronic Lymphocytic Leukemia in the Contemporary Era". PMID 26181643.
- ↑ V, Grubor; et al. (2009). "Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (ROMA)". PMID 18922857.
- ↑ 24.0 24.1 C, Schwaenen; et al. (2004). "Automated array-based genomic profiling in chronic lymphocytic leukemia: development of a clinical tool and discovery of recurrent genomic alterations". doi:10.1073/pnas.0304717101. PMC 327147. PMID 14730057.CS1 maint: PMC format (link)
- ↑ 25.0 25.1 25.2 25.3 Wg, Wierda; et al. (2017). "NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 1.2017". PMID 28275031.
- ↑ M, Dal Bo; et al. (2011). "13q14 deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia". PMID 21563234.
- ↑ 27.0 27.1 Sn, Malek (2013). "The biology and clinical significance of acquired genomic copy number aberrations and recurrent gene mutations in chronic lymphocytic leukemia". doi:10.1038/onc.2012.411. PMC 3676480. PMID 23001040.CS1 maint: PMC format (link)
- ↑ Pt, Greipp; et al. (2013). "Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1 and 11q22.3 have a very poor prognosis". doi:10.1111/bjh.12534. PMC 3907074. PMID 24032430.CS1 maint: PMC format (link)
- ↑ A, Cosson; et al. (2014). "14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma". PMID 24729385.
- ↑ 30.0 30.1 R, Ibbotson; et al. (2012). "Coexistence of trisomies of chromosomes 12 and 19 in chronic lymphocytic leukemia occurs exclusively in the rare IgG-positive variant". PMID 21788947.
- ↑ Sr, Gunn; et al. (2008). "The HemeScan test for genomic prognostic marker assessment in chronic lymphocytic leukemia". PMID 23495782.
- ↑ H, Parker; et al. (2016). "Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia". doi:10.1038/leu.2016.134. PMC 5023049. PMID 27282254.CS1 maint: PMC format (link)
- ↑ 33.0 33.1 Hagenkord, Jill M.; et al. (2010-03). "Array-based karyotyping for prognostic assessment in chronic lymphocytic leukemia: performance comparison of Affymetrix 10K2.0, 250K Nsp, and SNP6.0 arrays". The Journal of molecular diagnostics: JMD. 12 (2): 184–196. doi:10.2353/jmoldx.2010.090118. ISSN 1943-7811. PMC 2871725. PMID 20075210. Check date values in:
|date=(help) - ↑ Pfeifer, Dietmar; et al. (2007-02-01). "Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays". Blood. 109 (3): 1202–1210. doi:10.1182/blood-2006-07-034256. ISSN 0006-4971. PMID 17053054.
- ↑ 35.0 35.1 35.2 35.3 Edelmann, Jennifer; et al. (2012-12-06). "High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations". Blood. 120 (24): 4783–4794. doi:10.1182/blood-2012-04-423517. ISSN 1528-0020. PMID 23047824.
- ↑ Grygalewicz, Beata; et al. (2016). "Monoallelic and biallelic deletions of 13q14 in a group of CLL/SLL patients investigated by CGH Haematological Cancer and SNP array (8x60K)". Molecular Cytogenetics. 9: 1. doi:10.1186/s13039-015-0212-x. ISSN 1755-8166. PMC 4702365. PMID 26740820.
- ↑ Gunnarsson, Rebeqa; et al. (2011-08). "Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia". Haematologica. 96 (8): 1161–1169. doi:10.3324/haematol.2010.039768. ISSN 1592-8721. PMC 3148910. PMID 21546498. Check date values in:
|date=(help) - ↑ 38.0 38.1 38.2 Parker, H.; et al. (2011-03). "13q deletion anatomy and disease progression in patients with chronic lymphocytic leukemia". Leukemia. 25 (3): 489–497. doi:10.1038/leu.2010.288. ISSN 1476-5551. PMID 21151023. Check date values in:
|date=(help) - ↑ Lehmann, Sören; et al. (2008-03-15). "Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia". Cancer. 112 (6): 1296–1305. doi:10.1002/cncr.23270. ISSN 0008-543X. PMID 18246537.
- ↑ Ouillette, Peter; et al. (2011-11-01). "The prognostic significance of various 13q14 deletions in chronic lymphocytic leukemia". Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 17 (21): 6778–6790. doi:10.1158/1078-0432.CCR-11-0785. ISSN 1078-0432. PMC 3207001. PMID 21890456.
- ↑ 41.0 41.1 Stevens-Kroef, Marian Jpl; et al. (2014-01-09). "Identification of prognostic relevant chromosomal abnormalities in chronic lymphocytic leukemia using microarray-based genomic profiling". Molecular Cytogenetics. 7 (1): 3. doi:10.1186/1755-8166-7-3. ISSN 1755-8166. PMC 3905918. PMID 24401281.
- ↑ Saddler, Chris; et al. (2008-02-01). "Comprehensive biomarker and genomic analysis identifies p53 status as the major determinant of response to MDM2 inhibitors in chronic lymphocytic leukemia". Blood. 111 (3): 1584–1593. doi:10.1182/blood-2007-09-112698. ISSN 0006-4971. PMID 17971485.
- ↑ Pei, Jianming; et al. (2014-03). "Copy neutral loss of heterozygosity in 20q in chronic lymphocytic leukemia/small lymphocytic lymphoma". Cancer Genetics. 207 (3): 98–102. doi:10.1016/j.cancergen.2014.02.005. ISSN 2210-7762. PMC 4010307. PMID 24704113. Check date values in:
|date=(help) - ↑ Xu, Xinjie; et al. (2013-09). "The advantage of using SNP array in clinical testing for hematological malignancies--a comparative study of three genetic testing methods". Cancer Genetics. 206 (9–10): 317–326. doi:10.1016/j.cancergen.2013.09.001. ISSN 2210-7762. PMID 24269304. Check date values in:
|date=(help) - ↑ 45.0 45.1 Wierda, William G.; et al. (03 2017). "NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 1.2017". Journal of the National Comprehensive Cancer Network: JNCCN. 15 (3): 293–311. doi:10.6004/jnccn.2017.0030. ISSN 1540-1413. PMID 28275031. Check date values in:
|date=(help) - ↑ 46.0 46.1 Campregher, Paulo Vidal; et al. (2014-08). "Novel prognostic gene mutations identified in chronic lymphocytic leukemia and their impact on clinical practice". Clinical Lymphoma, Myeloma & Leukemia. 14 (4): 271–276. doi:10.1016/j.clml.2013.12.016. ISSN 2152-2669. PMID 24548608. Check date values in:
|date=(help) - ↑ 47.0 47.1 47.2 Strefford, Jonathan C. (2015-04). "The genomic landscape of chronic lymphocytic leukaemia: biological and clinical implications". British Journal of Haematology. 169 (1): 14–31. doi:10.1111/bjh.13254. ISSN 1365-2141. PMID 25496136. Check date values in:
|date=(help) - ↑ Alsolami, Reem; et al. (2013-06-01). "Clinical application of targeted and genome-wide technologies: can we predict treatment responses in chronic lymphocytic leukemia?". Personalized Medicine. 10 (4): 361–376. doi:10.2217/pme.13.33. ISSN 1741-0541. PMC 3943176. PMID 24611071.
- ↑ 49.0 49.1 49.2 Baliakas, P.; et al. (2015-02). "Recurrent mutations refine prognosis in chronic lymphocytic leukemia". Leukemia. 29 (2): 329–336. doi:10.1038/leu.2014.196. ISSN 1476-5551. PMID 24943832. Check date values in:
|date=(help) - ↑ 50.0 50.1 50.2 50.3 Rossi, Davide; et al. (2013-02-21). "Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia". Blood. 121 (8): 1403–1412. doi:10.1182/blood-2012-09-458265. ISSN 1528-0020. PMC 3578955. PMID 23243274.
- ↑ Rodríguez, David; et al. (2015-07-09). "Mutations in CHD2 cause defective association with active chromatin in chronic lymphocytic leukemia". Blood. 126 (2): 195–202. doi:10.1182/blood-2014-10-604959. ISSN 1528-0020. PMID 26031915.
- ↑ Wang, Lili; et al. (2011-12-29). "SF3B1 and other novel cancer genes in chronic lymphocytic leukemia". The New England Journal of Medicine. 365 (26): 2497–2506. doi:10.1056/NEJMoa1109016. ISSN 1533-4406. PMC 3685413. PMID 22150006.
- ↑ 53.0 53.1 Filip, Agata A. (2013-09). "New boys in town: prognostic role of SF3B1, NOTCH1 and other cryptic alterations in chronic lymphocytic leukemia and how it works". Leukemia & Lymphoma. 54 (9): 1876–1881. doi:10.3109/10428194.2013.769049. ISSN 1029-2403. PMID 23343182. Check date values in:
|date=(help) - ↑ Nabhan, Chadi; et al. (2015-10). "Predicting Prognosis in Chronic Lymphocytic Leukemia in the Contemporary Era". JAMA oncology. 1 (7): 965–974. doi:10.1001/jamaoncol.2015.0779. ISSN 2374-2445. PMID 26181643. Check date values in:
|date=(help) - ↑ Balatti, Veronica; et al. (2012-01-12). "NOTCH1 mutations in CLL associated with trisomy 12". Blood. 119 (2): 329–331. doi:10.1182/blood-2011-10-386144. ISSN 1528-0020. PMC 3257004. PMID 22086416.
- ↑ Del Giudice, Ilaria; et al. (2012-03). "NOTCH1 mutations in +12 chronic lymphocytic leukemia (CLL) confer an unfavorable prognosis, induce a distinctive transcriptional profiling and refine the intermediate prognosis of +12 CLL". Haematologica. 97 (3): 437–441. doi:10.3324/haematol.2011.060129. ISSN 1592-8721. PMC 3291600. PMID 22207691. Check date values in:
|date=(help) - ↑ Herling, Carmen Diana; et al. (07 21, 2016). "Complex karyotypes and KRAS and POT1 mutations impact outcome in CLL after chlorambucil-based chemotherapy or chemoimmunotherapy". Blood. 128 (3): 395–404. doi:10.1182/blood-2016-01-691550. ISSN 1528-0020. PMID 27226433. Check date values in:
|date=(help) - ↑ Ramsay, Andrew J.; et al. (2013-05). "POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia". Nature Genetics. 45 (5): 526–530. doi:10.1038/ng.2584. ISSN 1546-1718. PMID 23502782. Check date values in:
|date=(help) - ↑ Speedy, Helen E.; et al. (11 10, 2016). "Germ line mutations in shelterin complex genes are associated with familial chronic lymphocytic leukemia". Blood. 128 (19): 2319–2326. doi:10.1182/blood-2016-01-695692. ISSN 1528-0020. PMC 5271173. PMID 27528712. Check date values in:
|date=(help) - ↑ Mitsui, Takeki; et al. (2016-02). "SF3B1 and IGHV gene mutation status predict poor prognosis in Japanese CLL patients". International Journal of Hematology. 103 (2): 219–226. doi:10.1007/s12185-015-1912-z. ISSN 1865-3774. PMID 26588928. Check date values in:
|date=(help) - ↑ Quesada, Víctor; et al. (2011-12-11). "Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia". Nature Genetics. 44 (1): 47–52. doi:10.1038/ng.1032. ISSN 1546-1718. PMID 22158541.
- ↑ Wan, Youzhong; et al. (2013-06-06). "SF3B1 mutations in chronic lymphocytic leukemia". Blood. 121 (23): 4627–4634. doi:10.1182/blood-2013-02-427641. ISSN 1528-0020. PMC 3674664. PMID 23568491.
- ↑ Rossi, Davide; et al. (2014-04-03). "Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia". Blood. 123 (14): 2139–2147. doi:10.1182/blood-2013-11-539726. ISSN 1528-0020. PMC 4017291. PMID 24501221.
- ↑ Zenz, Thorsten; et al. (2010-10-10). "TP53 mutation and survival in chronic lymphocytic leukemia". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 28 (29): 4473–4479. doi:10.1200/JCO.2009.27.8762. ISSN 1527-7755. PMID 20697090.
- ↑ Stilgenbauer, Stephan; et al. (2014-05-22). "Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial". Blood. 123 (21): 3247–3254. doi:10.1182/blood-2014-01-546150. ISSN 1528-0020. PMID 24652989.
- ↑ Cosson, A.; et al. (07 2017). "Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1". Leukemia. 31 (7): 1625–1629. doi:10.1038/leu.2017.100. ISSN 1476-5551. PMID 28344316. Check date values in:
|date=(help) - ↑ Jain, Nitin; et al. (2015-07-23). "Initial treatment of CLL: integrating biology and functional status". Blood. 126 (4): 463–470. doi:10.1182/blood-2015-04-585067. ISSN 1528-0020. PMC 4624441. PMID 26065656.