Recurrent Genomic Alterations in Pediatric and Adult Central Nervous System Tumors Detected by Chromosomal Microarray
Recurrent Genomic Alterations in Pediatric and Adult Central Nervous System Tumors Detected by Chromosomal Microarray
Table 1: Pediatric CNS Tumors. Table derived from CGC CNS Workgroup 2015-2018.
| 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 |
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 |
| Angiocentric glioma | Aberrations involving 6q24-q25 | Fusions: MYB-QKI rearrangement/deletion (classic histology) Rearrangement: MYB alone (atypical histology) |
Generally indolent tumors; surgical resection can be curative | PMID:26829751; PMID:23633565; PMID:26778052 PMID:23583981 | |
| Ganglioglioma | Only 30% are abnormal by karyotype Gain: polysomy 7 | Mutations: BRAF V600E in 20-60% of cases (can be concurrent with CDKN2A homozygous deletion) Fusions: KIAA1549-BRAF |
Generally indolent tumors for which surgical resection can be curative | PMID:25461780; PMID:23583981; PMID:11996800 PMID:23609006; PMID:29880043 | |
| Low grade glioma, WHO grade II | Diffuse astrocytoma | No diagnostic aberrations | Rearrangement: MYBL1 truncating rearrangements and tandem duplication, FGFR1 rearrangements Mutation: FGFR1 |
Anaplastic features associated with decreased progression free survival | PMID:25664944; PMID:23633565; PMID:26061751 PMID:26824661; PMID:26004297; PMID:25461780 PMID:23583981 |
| Pleomorphic xanthoastrocytoma (PXA) | Polysomy 3, polysomy 7 observed; Loss: monosomy 9 / 9p deletion | Mutations: BRAF V600E in ~60%; TP53 (5%) Loss: CDKN2A/CDKN2B |
PMID:25461780; PMID:23583981; PMID:16909113; PMID:12484572 | ||
| Anaplastic astrocytoma, WHO grade III | IDH-mutant or IDH-wild type | Gain: 1q, 7/7q, 8q, 10p Loss: 6q, 9p, 10q, -11/11p, 12q, 13q, 14q, 17p, 19q, -22/22q |
IDH-wild type astrocytomas can be more clinically aggressive than those that are IDH-mutant | PMCID:1891902; PMID:26004297; PMID:25461780; PMID:24140581; PMCID:5323185; PMID:27230974 PMID:27196377; PMID:26061751; PMID:25962792; PMID:29687258 | |
| Other | Anaplastic PXA, WHO grade III / Ganglioglioma, WHO Grade III | Loss: monosomy 9 / 9p deletion, but no diagnostic findings | Mutation: BRAF V600E less common here than in PXA, grade II
Loss: CDKN2A/CDKN2B |
CDKN2A/CDKN2B loss may correlate with anaplastic histology | WHO CNS Tumors (2016) PMID:25318587; PMID:23096133; PMID:21274720 |
| Glioblastoma, WHO grade IV | IDH-mutant | Gain: 1q, 2q, 3q, 7, 16p, 17q, 21q
Loss: 6q, 8q, 9p, 9q, 10q, 13q, 17p, 22q Chromothripsis: observed |
Loss: PTEN, RB1, TP53, CDKN2A/B/C
Fusions: FGFR-TACC; NTRK fusions
Amplification: PDGFRA, MYCN, MET, CDK4, CDK6 (EGFR, MDM2 amp rare) |
Overall poor prognosis | PMID:25752754; PMID:25727226; PMID:26328271; PMID:22837387; PMID:25754088; PMID:25461780; PMCID:1891902; PMID:23417712; PMCID:5323185; PMID:29687258; PMID:20479398; PMID:24959384 |
| Diffuse midline glioma, H3 K27M mutant | Gain: 1q, 2, 7, 8 Loss: 10q |
Three molecular subgroups: MYCN subgroup: no mutations but chromothripsis leading to amp of MYCN and ID2 |
Overall poor prognosis regardless of subgroup | PMCID:3280796; PMID:24705254; PMID:24705252 PMID:27048880; PMID:26175967; PMID:24705251; PMID:28966033 | |
| EPENDYMOMA (in order of increasing WHO grade) |
DNA-based methylation classifies tumors across anatomical sites (posterior fossa, supratentorial, spinal), grades and age groups | Fusion: YAP1 fusions (supratentorial tumors) Mutation: NF2 (spinal tumors) |
Intracranial (in children, 90%) or spinal tumors; Histological distinction between WHO grade II and III is of questionable relevance; Prognostic differences among tumors suggested on the basis of methylation analysis | WHO CNS Tumors (2016) PMID:25965575; PMID:21627842; PMID:24939246; PMID:22516549 | |
| Classic ependymoma (no WHO grade assigned) | Gain: 1q, 5, 7, 9, 11, 18, 20 Loss: 1p, 3, -6/6q, 9p, 13q, 17, 22 |
Usually intracranial, spinal tumors (myxopapillary) are rare; 80% of pediatric tumors develop in posterior fossa (PF); Supratentorial tumors preferentially show monosomy 9; 1q gain is unfavorable prognostic indicator in PF tumors; spinal tumors associated with NF2 (germline); children have worse outcomes than adults | PMID:25965575; PMID:22338015; PMID:28371821 | ||
| Subependymoma, WHO grade I | Typically balanced genomes Loss: -6/6q in spinal tumors |
No diagnostic mutations | Favorable prognosis | WHO CNS Tumors (2016) PMID:21959044; PMID:21840481 | |
| Myxopapillary ependymoma, WHO grade I | Aneuploidy: multiple chromosomes lost and gained | Mutation: NF2 (including germline) in spinal tumors | Less common but more aggressive in children | PMID:25965575; PMCID:3991130; PMID:20425037; PMID:25957288; PMID:25965575; PMID:22516549 | |