Open AccessEpithelioid glioblastomas stratify into established diagnostic subsets upon integrated molecular analysis
Author(s) -
Korshunov Andrey,
Chavez Lukas,
Sharma Tanvi,
Ryzhova Marina,
Schrimpf Daniel,
Stichel Damian,
Capper David,
Sturm Dominik,
Kool Marcel,
Habel Antje,
KleinschmidtDeMasters Bette K.,
Rosenblum Marc,
Absalyamova Oksana,
Golanov Andrey,
Lichter Peter,
Pfister Stefan M.,
Jones David T.W.,
Perry Arie,
von Deimling Andreas
Publication year - 2018
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12566
Subject(s) - pdgfra , cdkn2a , smarcb1 , pathology , copy number analysis , glioblastoma , medicine , biology , oncology , cancer research , gene , copy number variation , cancer , genome , gist , genetics , stromal cell , chromatin remodeling , chromatin
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.