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

Table 1 - Pediatric Central Nervous System Tumors. Table derived from CGC CNS Workgroup 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 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
	Angiocentric glioma	Aberrations involving 6q24-q25	Fusions: MYB-QKI rearrangement/deletion (classic histology); Rearrangement: MYB alone (atypical histology); Amplification: MYB (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) Mutations: IDH1/2 (rare in pediatric GBM), KRAS, RAS pathway, RB1 pathway, TP53 pathway, FGFR1, H3.3/H3.1-K27M (exclusively in diffuse midline tumors), PDGFRA, NF1, SETD2, ATRX, DAXX	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 Chromothripsis: 2p	Three molecular subgroups: MYCN subgroup: no mutations but chromothripsis leading to amp of MYCN and ID2; Silent subgroup: no recurrent copy # changes, few mutations; H3-K27M subgroup: MYC, PDGFRA gains/amp; RB1, TP53 deletions Mutation: ACVR1, H3F3A, HIST1H3B, TP53 Loss: CDKN2A, PTEN, RB1, TP53 Amplification: MYC, MYCN, ID2, PDGFRA	Overall poor prognosis regardless of subgroup	PMCID:3280796; PMID:24705254; PMID:24705252 PMID:27048880; PMID:26175967; PMID:24705251; PMID:28966033