Table 1 Molecular testing for WHO 2016 CNS tumor entities / subgroups
From: A little piece of mind: best practices for brain tumor intraoperative consultation
Tumor type | Entity/subgroup-defining molecular alterations | Available clinical assays and tissue requirements | Additional testing to consider |
|---|---|---|---|
Diffuse glioma | IDH1/IDH2 mutations | IDH1 R132H IHC—FFPE US | ATRX and p53 IHC (ATRX loss and/or p53 overexpression characteristic of diffuse astrocytoma; also typically mutually exclusive from codeletion 1p/19q) |
IDH1 codon 132 and IDH2 codon 172 sequencing—FFPE scrolls or frozen tissue | |||
Histone H3 K27M mutations (midline tumors) | H3 K27M IHC—FFPE US (note: detects H3.3 and H3.1 mutation products) | ||
H3F3A or HIST1H3B/C sequencing—FFPE scrolls or frozen tissue | |||
Codeletion 1p/19q | 1p/19q FISH—FFPE US | ||
Array CGH/SNP array—FFPE scrolls or frozen tissue | |||
Medulloblastoma | WNT, SHH, group 3, group 4 molecular subgroups | β-Catenin, GAB1, YAP1 IHC—FFPE US | FISH assays for C17 alterations, monosomy 6, MYC or MYCN amplification—FFPE US |
Methylation array/gene expression profiling—FFPE scrolls or frozen tissue | Methylation array (or SNP array) for genome-wide assessment of copy number alterations—FFPE scrolls or frozen tissue | ||
TP53 mutation (for SHH subgroup) | p53 IHC—FFPE US (note: strong diffuse nuclear staining correlates well with TP53 mutation) | ||
TP53 sequencing—FFPE scrolls or frozen tissue | |||
CTNNB2 mutation (for confirmation WNT subgroup) | CTNNB2 sequencing—FFPE scrolls or frozen tissue (note: nuclear β-catenin staining by IHC correlates well with CTTNB2 mutation; sequencing is definitive) | ||
Other CNS embryonal tumors | C19MC amplification/fusion (ETMR, C19MC-altered) | C19MC FISH—FFPE US | |
INI1 and BRG1 inactivation (AT/RT) | INI1 and BRG1 IHC—FFPE US | ||
INI1 and BRG1 sequencing—FFPE scrolls or frozen tissue | |||
Ependymoma | Supratentorial-RELA fusion | L1CAM IHC—FFPE US (note: high correlation with RELA fusion, but not specific) | Posterior fossa ependymoma—H3K27me3 (trimethylation) IHC—FFPE US (note: PFE-group A = loss of nuclear staining) |
RELA and C11orf95 FISH—FFPE US (note: definitive testing) |
