Recurrent Genomic Alterations in Pediatric and Adult Central Nervous System Tumors Detected by Chromosomal Microarray

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Recurrent Genomic Alterations in Pediatric and Adult CNS Detected by Chromosomal Microarray (Literature Review)

Table 1 - Pediatric Central Nervous System Tumors. Table derived from Ligon et al., 2018 [ ] with permission from Cancer Genetics.

TUMOR SUBTYPES BROAD ABERRATIONS (>10Mb) FOCAL ABERRATIONS (>10Mb) CLINICAL FEATURES REFERENCES
GLIOMAS
Low grade glioma, WHO grade I Pilocytic astrocytoma/pilomyxoid astrocytoma Some tumors show polysomy 7; other polysomies more common in adult PA Fusions: KIAA1549-BRAF fusion (via 3'BRAF duplication), other BRAF partners reported; NTRK fusions (rare); FGFR1 fusions (rare); Mutations: BRAF V600E (particularly extra-cerebellar tumors); FGFR1 (midline PA); NF1 (esp. germline), other MAPK pathway mutations Loss: NF1 in optic pathway PA Classic PA are cerebellar (most commonly associated with BRAF duplication); PA in patients with germline NF1 alterations often develop as optic gliomas;Surgical resection can be curative; PMA generally more aggressive than PA; BRAF fusions and BRAF mutations generally are mutually exclusive PMID:19016743; PMCID:2761618; PMID:18716556 PMID:25461780 PMID:25664944; PMID:26378811 PMCID:3429698; PMID:23817572; PMID:23583981 PMID:18974108; PMID:23278243; PMID:21274720
AML including NK-AML CN-LOH 1p D 3
2 AML CN-LOH 2p DNMT3A D 3
3 NK-AML, sAML Loss 3p14.1 FOXP1 D 3
4 sAML, pAML CN-LOH 4q24 TET2 D 3
4 AML, NK-AML, sAML Loss 4q24 TET2 D, P 3
5 pAML, sAML Loss 5q D 1
6 AML including NK-AML CN-LOH 6p D 3
7 AML including NK-AML CN-LOH 7q EZH2 D 3
7 NK-AML, pAML, sAML Loss 7q EZH2, CUX1 D 1
8 AML with complex karyotype Amplification 8q24 MYC D, P 3
9 NK-AML, sAML CN-LOH 9p JAK2 D 3
11* AML with complex karyotype Amplification 11q23 MLL (KMT2A) D, P 3
11* AML CN-LOH 11p WT1 D 3
11 pAML, sAML, NK-AML CN-LOH 11q CBL D 3
12 AML, NK-AML, AML with complex karyotype, sAML Loss 12p13.2 ETV6 D 3
13* pAML, NK-AML, NPM1 mutated AML, FLT3-ITD positive AML, sAML CN-LOH 13q FLT3 D, P 2
16 NK-AML, AML with complex karyotype, pAML, sAML Loss 16q CBFB D 3
17 AML, NK-AML, pAML, sAML CN-LOH 17p TP53 D 3
17 sAML, NK-AML, AML with complex karyotype, de novo AML Loss 17p TP53 D, P 1
17 NK-AML, pAML Loss 17q11.2 NF1, SUZ12 D, P 3
19* AML, NK-AML, sAML CN-LOH 19q CEBPA D 3
20 sAML Loss 20q D 3
21* pAML, AML with complex karyotype Amplification 21q22 ERG, ETS2 D, P, T 3
21* AML, NK-AML, sAML CN-LOH 21q RUNX1 D 3
21* sAML Loss 21q22.12 RUNX1 D 3

D = diagnostic significance; P = prognostic significance; T = therapeutic significance. Classification of levels of evidence: Level 1 = WHO classification or professional practice guidelines; Level 2 = well-powered studies with consensus from experts in the field; Level 3 = multiple small studies without any contradicting data; Level 4 = individual small studies, case reports, preclinical studies.

Abrreviations: CMA = chromosomal microarray; CNA = copy number aberration; CN-LOH = copy-neutral loss-of-heterozygosity; AML = acute myeloid leukemia; NK-AML = normal karyotype AML; pAML = primary AML; and sAML = secondary AML.

The * indicates CNAs and CN-LOH regions that are predominantly seen in AML.

Reference

1. Xu X, Bryke C, Sukhanova M, Huxley E, Dash DP, Dixon-Mciver A, Fang M, Griepp PT, Hodge JC, Iqbal A, Jeffries S, Kanagal-Shamanna R, Quintero-Rivera F, Shetty S, Slovak ML, Yenamandra A, Lennon PA, Raca G. (2018). Assessing copy number abnormalities and copy-neutral loss-of-heterozygosity across the genome as best practice in diagnostic evaluation of acute myeloid leukemia: An evidence-based review from the cancer genomics consortium (CGC) myeloid neoplasms working group. Cancer Genet [Epub ahead of print], PMID 30344013.