Details

Autor(en) / Beteiligte

• 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

Titel

The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma

Ist Teil von

• Nature communications, 2018-05, Vol.9 (1), p.2087-11, Article 2087

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.