Format

Send to

Choose Destination
Brain Pathol. 2018 Sep;28(5):656-662. doi: 10.1111/bpa.12566. Epub 2017 Oct 30.

Epithelioid glioblastomas stratify into established diagnostic subsets upon integrated molecular analysis.

Author information

1
Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
2
Department of Neuropathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, Heidelberg 69120, Germany.
3
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
4
Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
5
NN Burdenko Neurosurgical Institute, 5-th Tverskaya_Yamskaya str. 16, Moscow, Russia.
6
Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg 69120, Germany.
7
Department of Pathology, University of Colorado Anschutz Medical Campus 12605 East 16th Avenue, Aurora, CO.
8
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
9
Division of Molecular Genetics (B060), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
10
Departments of Pathology and Neurological Surgery, Brain Tumor Research Center, University of California, 505 Parnassus Avenue, San Francisco, CA.

Abstract

Epithelioid glioblastoma (eGBM) is a newly defined and rare GBM variant in the current WHO 2016 classification. BRAF V600E mutation is overrepresented in these tumors and there is known some morphological overlap with anaplastic epithelioid PXA (ePXA). In order to further elucidate this diagnostic category, we molecularly characterized 64 pediatric and adult examples initially diagnosed as "eGBM." Tumors were analyzed using array based methylation and direct sequencing of the BRAF and TERT genes. Our results demonstrated considerable molecular and clinical heterogeneity among eGBM cohort. Methylation patterns, copy number alterations, and mutational analysis data, in combination with clinical findings disclosed three different, well established tumor subtypes: (i) PXA-like tumors with favorable prognosis, predominantly in children and young adults (38), (ii) IDHwt GBM-like tumors with poor prognosis, mainly occurring in older adults, albeit with more frequent BRAF mutations (17), and (iii) RTK1 pediatric GBM-like neoplasms of intermediate prognosis in children and young adults, associated with chromothripsis and frequent PDGFRA amplifications (9). We conclude that the histopathologically defined eGBM do not represent a single diagnostic entity, but rather at least three molecularly and biologically distinct categories. Therefore, additional molecular testing through genome-wide molecular profiling is recommended to further stratify these rare cases.

KEYWORDS:

cytogenetic prognostic; epithelioid; glioblastoma; methylation; pleomorphic xanthoastrocytoma; subgroup; survival

PMID:
28990704
DOI:
10.1111/bpa.12566
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center