Clinical multiplexed exome sequencing distinguishes adult oligodendroglial neoplasms from astrocytic and mixed lineage gliomas. Academic Article uri icon

Overview

abstract

  • Classifying adult gliomas remains largely a histologic diagnosis based on morphology; however astrocytic, oligodendroglial and mixed lineage tumors can display overlapping histologic features. We used multiplexed exome sequencing (OncoPanel) on 108 primary or recurrent adult gliomas, comprising 65 oligodendrogliomas, 28 astrocytomas and 15 mixed oligoastrocytomas to identify lesions that could enhance lineage classification. Mutations in TP53 (20/28, 71%) and ATRX (15/28, 54%) were enriched in astrocytic tumors compared to oligodendroglial tumors of which 4/65 (6%) had mutations in TP53 and 2/65 (3%) had ATRX mutations. We found that oligoastrocytomas harbored mutations in TP53 (80%, 12/15) and ATRX (60%, 9/15) at frequencies similar to pure astrocytic tumors, suggesting that oligoastrocytomas and astrocytomas may represent a single genetic or biological entity. p53 protein expression correlated with mutation status and showed significant increases in astrocytomas and oligoastrocytomas compared to oligodendrogliomas, a finding that also may facilitate accurate classification. Furthermore our OncoPanel analysis revealed that 15% of IDH1/2 mutant gliomas would not be detected by traditional IDH1 (p.R132H) antibody testing, supporting the use of genomic technologies in providing clinically relevant data. In all, our results demonstrate that multiplexed exome sequencing can support evaluation and classification of adult low-grade gliomas with a single clinical test.

publication date

  • September 30, 2014

Research

keywords

  • Astrocytoma
  • Biomarkers, Tumor
  • Brain Neoplasms
  • Cell Lineage
  • DNA Mutational Analysis
  • Exome
  • Genetic Testing
  • Mutation
  • Oligodendroglioma

Identity

PubMed Central ID

  • PMC4226668

Scopus Document Identifier

  • 84907998639

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.2342

PubMed ID

  • 25257301

Additional Document Info

volume

  • 5

issue

  • 18