Brain 17 Vienna

07.11.2017

Diffuse gliomas

What is the correct ‘integrated diagnosis‘ in the following case?

Histology: Oligoastrocytoma WHO grade: II Molecular markers: IDH2 mutant, 1p19q codeleted, TERT mutation, ATRX retained

• A1. Oligodendroglioma, WHO grade II, IDH2 mutant and 1p19q codeleted

• A2. Oligoastrocytoma, WHO grade II, IDH2 mutant and 1p19q codeleted

• A3. Astrocytoma, WHO grade II, IDH2 mutant and 1p19q codeleted

• A4. Oligodendroglioma, WHO grade II, NOS

A1 is correct

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Commonly used molecular techniques

Advanced molecular techniques

• IDH genes: • Step 1: mutation-specific IDH1 R132H antibody • Step 2: targeted IDH1/2 gene sequencing • Screening of all lower grade gliomas (II-III)

• Gene-panel sequencing

• Exome/RNA sequencing

• Screening of GBM, IV only in patients aged <55 years

• DNA methylation array • G-CIMP/IDH, copy numbers, MGMT

• 1p 19q chromosomal arms: • Multiplex ligation probe amplification • Fluorescence in situ hybridization

• CAVE: • Quality control / data standardization • DNA quality of FFPE tissues

• MGMT promoter methylation: • Pyrosequencing • Methylation-specific PCR

CAVE:Analytical test performance, interlab comparisons

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Glioblastoma

Glioblastoma

• New variant: Epitheloid glioblastoma

• Glioblastoma, IDH-wildtype (about 90% of cases)

• Stratifies into established diagnostic subsets upon molecular diagnosis

• Glioblastoma, IDH-mutant (about 10% of cases) corresponds closely to secondary glioblastoma • Glioblastoma, NOS in cases without full IDH assessment • Sequencing required for all patients > 55 years of age

BRAF V600E

Louiset al, Acta Neuropath 2016

Variant = Subtype of an entity of clinical utility

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