Open AccessWhole‐exome sequencing revealed mutational profiles of giant cell glioblastomas
Author(s) -
Shi Zhifeng,
Li Kay KaWai,
Kwan Johnny Sheung Him,
Yang Rui Ryan,
Aibaidula Abudumijiti,
Tang Qisheng,
Bao Yifeng,
Mao Ying,
Chen Hong,
Ng HoKeung
Publication year - 2019
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.12720
Subject(s) - biology , exome sequencing , pten , genetics , atrx , msh6 , mutation , somatic hypermutation , cancer research , exome , mlh1 , gene , germline mutation , dna mismatch repair , dna repair , apoptosis , b cell , pi3k/akt/mtor pathway , antibody
Abstract Giant cell glioblastoma (gcGBM) is a rare histological variant of GBM, accounting for about 1% of all GBM. The prognosis is poor generally though gcGBM does slightly better than the other IDH‐wild‐type GBM. Because of the rarity of the cases, there has been no comprehensive molecular analysis of gcGBM. Previously, single‐gene study identified genetic changes in TP53, PTEN and TERT promoter mutation in gcGBM. In this report, we performed whole‐exome sequencing (WES) to identify somatically acquired mutations and copy number variations (CNVs) in 10 gcGBM genomes. We also examined TERT promoter mutation and MGMT methylation in our cohort. On top of the reported mutations, WES revealed ATRX, PIK3R1, RB1 and SETD2 as the recurrent mutations in gcGBM. Notably, one tumor harbored a mutation in MutS homolog 6 (MSH6) that is a key mismatch repair (MMR) gene. This tumor demonstrated hypermutation phenotype and showed an increased number of somatic mutations. TERT promoter mutation and MGMT methylation were observed in 20% and 40% of our samples, respectively. In conclusion, we described relevant mutation profiling for developing future targeted therapies in gcGBM.