Beyond IDH-Mutation: Emerging Molecular Diagnostic and Prognostic Features in Adult Diffuse Gliomas
Abstract
:1. Introduction
2. IDH-Mutant Lower-Grade Astrocytoma
3. Oligodendroglioma
4. IDH-Mutant Glioblastoma
5. IDH-Wildtype Lower-Grade Astrocytoma
6. IDH-Wildtype Glioblastoma
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Factor | Details | Reference |
---|---|---|
IDH1/2 mutation | Definitional | [4,5,7] |
1p/19q co-deletion | Incompatible with diagnosis | [4] |
19q | Loss of 19q chromosomal arm correlates with better outcome | [54] |
Total copy number variation (CNV) | Elevated CNV correlates with worse outcome | [41,49,52] |
CDK4 | Focal amplification correlates with worse outcome | [43,44,45,50,52] |
CDKN2A | Homozygous deletion correlates with worse outcome, grade IV equivalent (cIMPACT-NOW update 5) | [48,49,50,52,53] |
PDGFRA, PIK3R1, PIK3CA | Alteration correlates with worse outcome | [45,50,75] |
MYC/MYCN | Focal amplification correlates with worse outcome | [49,60] |
Nestin | IHC overexpression correlates with worse outcome | [61] |
Factor | Details | Reference |
---|---|---|
IDH1/2 mutation | Definitional | [4,5,7] |
1p/19q co-deletion | Definitional | [4,76,80] |
TP53, ATRX | Mutation in either gene inconsistent with diagnosis | [4,6] |
Total copy number variation (CNV) | Modestly elevated CNV correlates with worse outcome | [92] |
Total mutation burden | Elevated mutation burden (>1 mut/MB; >30 total exomic mutations) correlates with worse outcome | [92] |
1q & 19p | Simultaneous polysomy is correlated with worse outcome | [95,96,97,98] |
CDKN2A | Homozygous deletion is correlated with worse outcome in anaplastic oligodendrogliomas | [94] |
ARID1, NOTCH1, PIK3CA, and PIK3R1 | Alterations in genes in Notch and PI3K pathways are associated with worse outcome | [36,45,93] |
Factor | Details | Reference |
---|---|---|
IDH1/2 mutation | Definitional | [4,5,7] |
1p/19q co-deletion | Incompatible with diagnosis | [4] |
MGMT | Promoter methylation predicts improved response to temozolomide | [122,123] |
CCND2 | Amplification is correlated with better clinical outcome | [115] |
Total copy number variation (CNV) | Elevated CNV correlates with worse clinical outcome than IDH-mutant lower-grade gliomas, however, no in-group effects | [52,67] |
CDK4/MDM2 | Co-amplification is correlated with worse clinical outcome | [120,121] |
PDGFRA | Amplification is correlated with worse clinical outcome | [75] |
CDKN2A | Homozygous deletion is correlated with worse clinical outcome, especially when combined with MET amplification | [47,72,94] |
Factor | Details | Reference |
---|---|---|
IDH1/2 mutation | Incompatible with diagnosis | [4,5,7] |
1p/19q co-deletion | Incompatible with diagnosis | [4] |
Total copy number variation (CNV) | Elevated CNV correlates with worse clinical outcome than IDH-mutant lower- grade gliomas, however, no significant in-group effects | [52,127,129] |
EGFR amplification, 7+/10−, TERTp mutation | Alteration of any of these factors correlates with worse clinical outcome; grade IV equivalent (cIMPACT-NOW update 3) | [126,129,130,131] |
PTEN | Deletion correlates with worse clinical outcome | [136] |
Nestin | IHC overexpression correlates with worse outcome | [61] |
Factor | Details | Reference |
---|---|---|
IDH1/2 mutation | Incompatible with diagnosis | [4,5,7] |
1p/19q co-deletion | Incompatible with diagnosis | [4] |
MGMT | Promoter methylation predicts improved response to temozolomide, especially in the presence of TERTp mutation | [122,123,143,144,145,148] |
Chromosomes 19 & 20 | Co-gain correlates with better clinical outcome | [129,142] |
Chromosomes 1 & 19 | Isolated gain of either chromosome, in the absence of CDK4/MDM2 co- amplification correlates with better clinical outcome | [139] |
BRAF (V600E) | Mutation is correlated with better outcome | [152,153] |
EGFR amplification, 7+/10−, TERTp mutation | Alteration of any of these factors correlates with worse clinical outcome; GBM-C0 status correlates with better clinical outcome | [129] |
Total copy number variation (CNV) | Elevated CNV correlates with worse clinical outcome than IDH-mutant lower- grade gliomas, however, no in-group effects | [52,129] |
CDK4/MDM2 | Co-amplification is correlated with worse clinical outcome | [120,121,139] |
EGFR/PTEN/CDKN2A | Co-alterations of these three genes is correlated with worse clinical outcome | [141] |
PIK3CA | Mutations are correlated with worse clinical outcome | [140] |
H3K27M | Mutation in midline glioma correlates with worse clinical outcome; grade IV equivalent (cIMPACT-NOW update 2) | [169,173,174,175,177] |
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Mirchia, K.; Richardson, T.E. Beyond IDH-Mutation: Emerging Molecular Diagnostic and Prognostic Features in Adult Diffuse Gliomas. Cancers 2020, 12, 1817. https://doi.org/10.3390/cancers12071817
Mirchia K, Richardson TE. Beyond IDH-Mutation: Emerging Molecular Diagnostic and Prognostic Features in Adult Diffuse Gliomas. Cancers. 2020; 12(7):1817. https://doi.org/10.3390/cancers12071817
Chicago/Turabian StyleMirchia, Kanish, and Timothy E. Richardson. 2020. "Beyond IDH-Mutation: Emerging Molecular Diagnostic and Prognostic Features in Adult Diffuse Gliomas" Cancers 12, no. 7: 1817. https://doi.org/10.3390/cancers12071817