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