Format

Send to

Choose Destination
See comment in PubMed Commons below
Oncotarget. 2014 Sep 30;5(18):8083-92.

Clinical multiplexed exome sequencing distinguishes adult oligodendroglial neoplasms from astrocytic and mixed lineage gliomas.

Author information

1
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
2
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
3
Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
4
Kravis Center for Molecular Oncology & Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
5
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. Department of Pathology, Harvard Medical School, Boston, MA, USA.
6
Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
7
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Pathology, Harvard Medical School, Boston, MA, USA.

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.

PMID:
25257301
PMCID:
PMC4226668
DOI:
10.18632/oncotarget.2342
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Impact Journals, LLC Icon for PubMed Central
    Loading ...
    Support Center