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Recurrent Genomic Alterations in Pediatric and Adult Central Nervous System Tumors Detected by Chromosomal Microarray (view source)

Revision as of 07:27, 16 November 2018

63 bytes added , 07:27, 16 November 2018

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| 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

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| '''Fusions:''' KIAA1549-BRAF fusion (via 3'BRAF duplication), other BRAF partners reported; NTRK fusions (rare); FGFR1 fusions (rare)

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'''Mutations:''' BRAF V600E (particularly extra-cerebellar tumors); FGFR1 (midline PA); NF1 (esp. germline), other MAPK pathway mutations

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'''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

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| Angiocentric glioma

| Aberrations involving 6q24-q25

−

| '''Fusions:''' MYB-QKI rearrangement/deletion (classic histology); '''Rearrangement:''' MYB alone (atypical histology); '''Amplification:''' MYB (atypical histology)

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| '''Fusions:''' MYB-QKI rearrangement/deletion (classic histology)

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'''Rearrangement:''' MYB alone (atypical histology)

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'''Amplification:''' MYB (atypical histology)

| Generally indolent tumors; surgical resection can be curative

| PMID:26829751; PMID:23633565; PMID:26778052 PMID:23583981

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| 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

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| '''Mutations:''' BRAF V600E in 20-60% of cases (can be concurrent with CDKN2A homozygous deletion)

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'''Fusions:''' KIAA1549-BRAF

| Generally indolent tumors for which surgical resection can be curative

| PMID:25461780; PMID:23583981; PMID:11996800 PMID:23609006; PMID:29880043

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|Diffuse astrocytoma

|No diagnostic aberrations

−

| '''Rearrangement:''' MYBL1 truncating rearrangements and tandem duplication, FGFR1 rearrangements; '''Mutation:''' FGFR1

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| '''Rearrangement:''' MYBL1 truncating rearrangements and tandem duplication, FGFR1 rearrangements

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'''Mutation:''' FGFR1

| Anaplastic features associated with decreased progression free survival

| PMID:25664944; PMID:23633565; PMID:26061751 PMID:26824661; PMID:26004297; PMID:25461780 PMID:23583981

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| Pleomorphic xanthoastrocytoma (PXA)

| Polysomy 3, polysomy 7 observed; '''Loss:''' monosomy 9 / 9p deletion

−

| '''Mutations:''' BRAF V600E in ~60%; TP53 (5%); '''Loss:''' CDKN2A/CDKN2B

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| '''Mutations:''' BRAF V600E in ~60%; TP53 (5%)

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'''Loss:''' CDKN2A/CDKN2B

|

| PMID:25461780; PMID:23583981; PMID:16909113; PMID:12484572

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| 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

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| '''Gain:''' 1q, 7/7q, 8q, 10p

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'''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

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| 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

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| '''Mutation:''' BRAF V600E less common here than in PXA, grade II

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'''Loss:''' CDKN2A/CDKN2B

| CDKN2A/CDKN2B loss may correlate with anaplastic histology

| WHO CNS Tumors (2016), PMID:25318587; PMID:23096133; PMID:21274720

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|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

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|'''Gain:''' 1q, 2q, 3q, 7, 16p, 17q, 21q

−

|'''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

+

'''Loss:''' 6q, 8q, 9p, 9q, 10q, 13q, 17p, 22q

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''' Chromothripsis:''' observed

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|'''Loss:''' PTEN, RB1, TP53, CDKN2A/B/C

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'''Fusions:''' FGFR-TACC; NTRK fusions

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'''Amplification:''' PDGFRA, MYCN, MET, CDK4, CDK6 (EGFR, MDM2 amp rare)

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'''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

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|Diffuse midline glioma, H3 K27M mutant

|

−

|'''Gain:''' 1q, 2, 7, 8 '''Loss:''' 10q '''Chromothripsis:''' 2p

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|'''Gain:''' 1q, 2, 7, 8

−

|'''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

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'''Loss:''' 10q

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'''Chromothripsis:''' 2p

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|'''Three molecular subgroups:'''

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'''MYCN subgroup:''' no mutations but chromothripsis leading to amp of MYCN and ID2

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'''Silent subgroup:''' no recurrent copy # changes, few mutations

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'''H3-K27M subgroup:''' MYC, PDGFRA gains/amp; RB1, TP53 deletions

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'''Mutation:''' ACVR1, H3F3A, HIST1H3B, TP53 '''Loss:''' CDKN2A, PTEN, RB1, TP53

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'''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

Jennifer.Hauenstein

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