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.
- The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma.
- Paper ID
- The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, 27710, NC, USA.
Nature communications, 2018;9(1):2087
PMID: 29802247 (view at PubMed or Europe PMC)
- 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