GRCh38 · COSMIC v92

Summary

This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference
The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma.
Paper ID
COSP45424
Authors
Diplas BH, He X, Brosnan-Cashman JA, Liu H, Chen LH, Wang Z, Moure CJ, Killela PJ, Loriaux DB, Lipp ES, Greer PK, Yang R, Rizzo AJ, Rodriguez FJ, Friedman AH, Friedman HS, Wang S, He Y, McLendon RE, Bigner DD, Jiao Y, Waitkus MS, Meeker AK and Yan H
Affiliation
The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, 27710, NC, USA.
Journal
Nature communications, 2018;9(1):2087
ISSN: 2041-1723
PMID: 29802247 (view at PubMed or Europe PMC)
Abstract
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<sup>WT</sup>-IDH<sup>WT</sup> glioblastomas, do not have well-established genetic biomarkers or defined mechanisms of telomere maintenance. Here we report the genetic landscape of TERTp<sup>WT</sup>-IDH<sup>WT</sup> 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<sup>WT</sup>-TERT<sup>SV</sup>), and an ALT-positive subgroup (IDH<sup>WT</sup>-ALT) with mutations in ATRX or SMARCAL1.
Paper Status
Curated