Difference between revisions of "Recurrent Genomic Alterations in Pediatric and Adult Central Nervous System Tumors Detected by Chromosomal Microarray"
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| Pilocytic astrocytoma/pilomyxoid astrocytoma | | Pilocytic astrocytoma/pilomyxoid astrocytoma | ||
| Some tumors show polysomy 7; other polysomies more common in adult PA | | 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) | + | | '''Fusions:''' KIAA1549-BRAF fusion (via 3'BRAF duplication), other BRAF partners reported; NTRK fusions (rare); FGFR1 fusions (rare) <br> |
| + | '''Mutations:''' BRAF V600E (particularly extra-cerebellar tumors); FGFR1 (midline PA); NF1 (esp. germline), other MAPK pathway mutations <br> | ||
| + | '''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 | | 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 | | 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 | | Angiocentric glioma | ||
| Aberrations involving 6q24-q25 | | Aberrations involving 6q24-q25 | ||
| − | | '''Fusions:''' MYB-QKI rearrangement/deletion (classic histology) | + | | '''Fusions:''' MYB-QKI rearrangement/deletion (classic histology)<br> |
| + | '''Rearrangement:''' MYB alone (atypical histology)<br> | ||
| + | '''Amplification:''' MYB (atypical histology) | ||
| Generally indolent tumors; surgical resection can be curative | | Generally indolent tumors; surgical resection can be curative | ||
| PMID:26829751; PMID:23633565; PMID:26778052 PMID:23583981 | | PMID:26829751; PMID:23633565; PMID:26778052 PMID:23583981 | ||
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| Ganglioglioma | | Ganglioglioma | ||
| Only 30% are abnormal by karyotype '''Gain:''' polysomy 7 | | Only 30% are abnormal by karyotype '''Gain:''' polysomy 7 | ||
| − | | '''Mutations:''' BRAF V600E in 20-60% of cases (can be concurrent with CDKN2A homozygous deletion) | + | | '''Mutations:''' BRAF V600E in 20-60% of cases (can be concurrent with CDKN2A homozygous deletion)<br> |
| + | '''Fusions:''' KIAA1549-BRAF | ||
| Generally indolent tumors for which surgical resection can be curative | | Generally indolent tumors for which surgical resection can be curative | ||
| PMID:25461780; PMID:23583981; PMID:11996800 PMID:23609006; PMID:29880043 | | PMID:25461780; PMID:23583981; PMID:11996800 PMID:23609006; PMID:29880043 | ||
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|Diffuse astrocytoma | |Diffuse astrocytoma | ||
|No diagnostic aberrations | |No diagnostic aberrations | ||
| − | | '''Rearrangement:''' MYBL1 truncating rearrangements and tandem duplication, FGFR1 rearrangements | + | | '''Rearrangement:''' MYBL1 truncating rearrangements and tandem duplication, FGFR1 rearrangements<br> |
| + | '''Mutation:''' FGFR1 | ||
| Anaplastic features associated with decreased progression free survival | | Anaplastic features associated with decreased progression free survival | ||
| PMID:25664944; PMID:23633565; PMID:26061751 PMID:26824661; PMID:26004297; PMID:25461780 PMID:23583981 | | PMID:25664944; PMID:23633565; PMID:26061751 PMID:26824661; PMID:26004297; PMID:25461780 PMID:23583981 | ||
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| Pleomorphic xanthoastrocytoma (PXA) | | Pleomorphic xanthoastrocytoma (PXA) | ||
| Polysomy 3, polysomy 7 observed; '''Loss:''' monosomy 9 / 9p deletion | | Polysomy 3, polysomy 7 observed; '''Loss:''' monosomy 9 / 9p deletion | ||
| − | | '''Mutations:''' BRAF V600E in ~60%; TP53 (5%) | + | | '''Mutations:''' BRAF V600E in ~60%; TP53 (5%)<br> |
| + | '''Loss:''' CDKN2A/CDKN2B | ||
| | | | ||
| PMID:25461780; PMID:23583981; PMID:16909113; PMID:12484572 | | PMID:25461780; PMID:23583981; PMID:16909113; PMID:12484572 | ||
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| Anaplastic astrocytoma, WHO grade III | | Anaplastic astrocytoma, WHO grade III | ||
| IDH-mutant or IDH-wild type | | 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 | + | | '''Gain:''' 1q, 7/7q, 8q, 10p<br> |
| + | '''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 | | 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 | | Anaplastic PXA, WHO grade III / Ganglioglioma, WHO Grade III | ||
| '''Loss:''' monosomy 9 / 9p deletion, but no diagnostic findings | | '''Loss:''' monosomy 9 / 9p deletion, but no diagnostic findings | ||
| − | | '''Mutation:''' BRAF V600E less common here than in PXA, grade II '''Loss:''' CDKN2A/CDKN2B | + | | '''Mutation:''' BRAF V600E less common here than in PXA, grade II |
| + | '''Loss:''' CDKN2A/CDKN2B | ||
| CDKN2A/CDKN2B loss may correlate with anaplastic histology | | CDKN2A/CDKN2B loss may correlate with anaplastic histology | ||
| WHO CNS Tumors (2016), PMID:25318587; PMID:23096133; PMID:21274720 | | WHO CNS Tumors (2016), PMID:25318587; PMID:23096133; PMID:21274720 | ||
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|Glioblastoma, WHO grade IV | |Glioblastoma, WHO grade IV | ||
|IDH-mutant | |IDH-mutant | ||
| − | |'''Gain:''' 1q, 2q, 3q, 7, 16p, 17q, 21q '''Loss:''' 6q, 8q, 9p, 9q, 10q, 13q, 17p, 22q ''' Chromothripsis:''' observed | + | |'''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 |
| + | ''' Chromothripsis:''' observed | ||
| + | |'''Loss:''' PTEN, RB1, TP53, CDKN2A/B/C | ||
| + | '''Fusions:''' FGFR-TACC; NTRK fusions | ||
| + | '''Amplification:''' PDGFRA, MYCN, MET, CDK4, CDK6 (EGFR, MDM2 amp rare)<br> | ||
| + | '''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 | | 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 | |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 | |Diffuse midline glioma, H3 K27M mutant | ||
| | | | ||
| − | |'''Gain:''' 1q, 2, 7, 8 '''Loss:''' 10q '''Chromothripsis:''' 2p | + | |'''Gain:''' 1q, 2, 7, 8<br> |
| − | |'''Three molecular subgroups:''' '''MYCN subgroup:''' no mutations but chromothripsis leading to amp of MYCN and ID2 | + | '''Loss:''' 10q<br> |
| + | '''Chromothripsis:''' 2p | ||
| + | |'''Three molecular subgroups:''' <br> | ||
| + | '''MYCN subgroup:''' no mutations but chromothripsis leading to amp of MYCN and ID2<br> | ||
| + | '''Silent subgroup:''' no recurrent copy # changes, few mutations<br> | ||
| + | '''H3-K27M subgroup:''' MYC, PDGFRA gains/amp; RB1, TP53 deletions<br> | ||
| + | '''Mutation:''' ACVR1, H3F3A, HIST1H3B, TP53 '''Loss:''' CDKN2A, PTEN, RB1, TP53<br> | ||
| + | '''Amplification:''' MYC, MYCN, ID2, PDGFRA | ||
|Overall poor prognosis regardless of subgroup | |Overall poor prognosis regardless of subgroup | ||
|PMCID:3280796; PMID:24705254; PMID:24705252 PMID:27048880; PMID:26175967; PMID:24705251; PMID:28966033 | |PMCID:3280796; PMID:24705254; PMID:24705252 PMID:27048880; PMID:26175967; PMID:24705251; PMID:28966033 | ||
Revision as of 07:27, 16 November 2018
==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 |
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 |