Version May 2024
| Test | Method(s) of testing | Clinical implications and notes |
| IDH1/2 mutation | IHC for R132H-mutant IDH1*, sequencing of IDH1/2 | IDH1 IHC is required for all diffuse gliomas; when negative, sequencing of IDH1/2 should be prioritized for grade 2 and 3 gliomas and for glioblastoma in patients <55 years old; IDH mutations confer improved prognosis across all tumor grades. |
| MGMT promotor methylation | Methylation-specific PCR, array-based methylation assay | Methylation confers improved prognosis in high-grade gliomas and is predictive of improved responsiveness to alkylating-agent chemotherapy; no diagnostic value. |
| 1p/19q codeletion | FISH, LOH assay, aCGH, MLPA, PCR-based | Required for diffuse gliomas with oligodendroglial component; not routinely performed on glioblastoma specimens; indicated when oligodendroglial pattern predominates to help distinguish between glioblastoma and grade 3 oligodendroglioma; in the absence of an IDH mutation, codeletion by FISH should raise suspicion for partial or incomplete deletions, which are associated with some IDH-wildtype astrocytomas and a worse prognosis. |
| ATRX mutations | IHC for nuclear ATRX expression or sequencing | Loss of nuclear staining indicates the presence of an ATRX mutation, strongly associated with astrocytic lineage; ATRX mutations are mutually exclusive with 1p/19q codeletion but should not be used as a substitute for 1p/19q testing. |
| TERT promotor mutations | Sequencing | TERT mutations occur in IDH-wildtype diffuse astrocytomas and in IDH-mutant 1p/19q-codeleted oligodendrogliomas; in IDH-wildtype astrocytomas, TERT mutations are associated with poor prognosis and establish a diagnosis of glioblastoma independent of histologic features. |
| TP53 | IHC for mutant p53 | Mutant p53 staining is present in vast majority of astrocytic tumors but is not entirely sensitive or specific for astrocytic differentiation; no independent clinical or prognostic implications beyond assisting in pathologic diagnosis. |
| EGFR amplification and mutations | FISH, aCGH, sequencing | EGFR amplification is specific but not sensitive for glioblastoma; results may be relevant for clinical trials but no current therapeutic implications. In IDH-wildtype astrocytomas, EGFR amplification establishes a diagnosis of glioblastoma independent of histologic features. |
| Gain of chromosome 7/loss of 10q | FISH, aCGH | Combination of tri/polysomy 7 and LOH 10q in an IDH-wildtype diffuse astrocytoma is associated with aggressive clinical course and establishes a diagnosis of glioblastoma independent of histologic features; often seen along with TERT mutations and EGFR amplification. |
| PTEN mutations | Sequencing | Occurs in 20 to 30% of glioblastomas, as a rule accompanied by LOH 10q; may be relevant for clinical trials but has low diagnostic value and no current therapeutic implications. |
| BRAF V600E mutations | IHC for V600E-mutant BRAF or BRAF sequencing | Rare in glioblastoma and adult low-grade glioma (<5%) but has clinical trial and potential therapeutic implications. |
| Histone H3F3A and HIST1H3B mutations | IHC for K27M and G34 mutations, sequencing | K27M mutations mostly found in pediatric and young adult midline gliomas; young adult high-grade gliomas of the cortex may have H3F3A G34R/V mutations, usually combined with ATRX and TP53 mutations; usually associated with poor prognosis. |
| CDKN2A/B deletion | FISH, aCGH, sequencing | Negative prognostic marker when present in IDH-mutant diffuse gliomas; in IDH-mutant astrocytoma, CDKN2A/B deletion establishes the tumor as grade 4, even in the absence of high-grade histology. |
| NTRK fusions | FISH, sequencing fusion assays | Rare in adult gliomas but potentially treatable with TRK inhibitors. |
IDH1/2: isocitrate dehydrogenase type 1 or type 2; IHC: immunohistochemistry; MGMT: O6-methylguanine-DNA methyltransferase; PCR: polymerase chain reaction; FISH: fluorescence in situ hybridization; LOH: loss of heterozygosity; aCGH: array comparative genomic hybridization; MLPA: multiplex ligation-dependent probe amplification; ATRX: alpha-thalassemia/mental retardation syndrome X-linked; TERT: telomerase reverse transcriptase; EGFR: epidermal growth factor receptor; PTEN: phosphatase and tensin homolog; CDKN2A/B: cyclin-dependent kinase inhibitor 2A/B; NTRK: neurotrophic receptor tyrosine kinase.
* Most common IDH mutation in diffuse gliomas (approximately 90%).آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
