The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma

The majority of glioblastomas can be classified into molecular subgroups based on mutations in the TERT promoter (TERTp) and isocitrate dehydrogenase 1 or 2 (IDH). These molecular subgroups utilize distinct genetic mechanisms of telomere maintenance, either TERTp mutation leading to telomerase activ...

Full description

Saved in:

Bibliographic Details
Published in:	Nature communications 2018-05, Vol.9 (1), p.2087-11, Article 2087
Main Authors:	Diplas, Bill H, He, Xujun, Brosnan-Cashman, Jacqueline A, Liu, Heng, Chen, Lee H, Wang, Zhaohui, Moure, Casey J, Killela, Patrick J, Loriaux, Daniel B, Lipp, Eric S, Greer, Paula K, Yang, Rui, Rizzo, Anthony J, Rodriguez, Fausto J, Friedman, Allan H, Friedman, Henry S, Wang, Sizhen, He, Yiping, McLendon, Roger E, Bigner, Darell D, Jiao, Yuchen, Waitkus, Matthew S, Meeker, Alan K, Yan, Hai
Format:	Article
Language:	eng
Subjects:	Activation Adolescent Adult Aged Aged, 80 and over Biomarkers Brain cancer Brain Neoplasms - genetics Brain Neoplasms - metabolism Brain Neoplasms - pathology Cell Line, Tumor Chromosome rearrangements Chromosomes DNA Helicases - genetics DNA Helicases - metabolism Female Genomics - methods Glioblastoma Glioblastoma - genetics Glioblastoma - metabolism Glioblastoma - pathology HEK293 Cells HeLa Cells Humans Isocitrate dehydrogenase Isocitrate Dehydrogenase - genetics Isocitrate Dehydrogenase - metabolism Male Middle Aged Molecular chains Mutation Phenotypes Promoter Regions, Genetic - genetics Subgroups Survival Analysis Telomerase Telomerase - genetics Telomere Homeostasis Telomeres Tumors Young Adult
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The majority of glioblastomas can be classified into molecular subgroups based on mutations in the TERT promoter (TERTp) and isocitrate dehydrogenase 1 or 2 (IDH). These molecular subgroups utilize distinct genetic mechanisms of telomere maintenance, either TERTp mutation leading to telomerase activation or ATRX-mutation leading to an alternative lengthening of telomeres phenotype (ALT). However, about 20% of glioblastomas lack alterations in TERTp and IDH. These tumors, designated TERTp -IDH glioblastomas, do not have well-established genetic biomarkers or defined mechanisms of telomere maintenance. Here we report the genetic landscape of TERTp -IDH glioblastoma and identify SMARCAL1 inactivating mutations as a novel genetic mechanism of ALT. Furthermore, we identify a novel mechanism of telomerase activation in glioblastomas that occurs via chromosomal rearrangements upstream of TERT. Collectively, our findings define novel molecular subgroups of glioblastoma, including a telomerase-positive subgroup driven by TERT-structural rearrangements (IDH -TERT ), and an ALT-positive subgroup (IDH -ALT) with mutations in ATRX or SMARCAL1.
ISSN:	2041-1723 2041-1723