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The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma.

Publication ,  Journal Article
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; Wang, S ...
Published in: Nat Commun
May 25, 2018

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 TERTpWT-IDHWT glioblastomas, do not have well-established genetic biomarkers or defined mechanisms of telomere maintenance. Here we report the genetic landscape of TERTpWT-IDHWT 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 (IDHWT-TERTSV), and an ALT-positive subgroup (IDHWT-ALT) with mutations in ATRX or SMARCAL1.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

May 25, 2018

Volume

9

Issue

1

Start / End Page

2087

Location

England

Related Subject Headings

  • Young Adult
  • Telomere Homeostasis
  • Telomerase
  • Survival Analysis
  • Promoter Regions, Genetic
  • Mutation
  • Middle Aged
  • Male
  • Isocitrate Dehydrogenase
  • Humans
 

Citation

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Diplas, B. H., He, X., Brosnan-Cashman, J. A., Liu, H., Chen, L. H., Wang, Z., … Yan, H. (2018). The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma. Nat Commun, 9(1), 2087. https://doi.org/10.1038/s41467-018-04448-6
Diplas, Bill H., Xujun He, Jacqueline A. Brosnan-Cashman, Heng Liu, Lee H. Chen, Zhaohui Wang, Casey J. Moure, et al. “The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma.Nat Commun 9, no. 1 (May 25, 2018): 2087. https://doi.org/10.1038/s41467-018-04448-6.
Diplas BH, He X, Brosnan-Cashman JA, Liu H, Chen LH, Wang Z, et al. The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma. Nat Commun. 2018 May 25;9(1):2087.
Diplas, Bill H., et al. “The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma.Nat Commun, vol. 9, no. 1, May 2018, p. 2087. Pubmed, doi:10.1038/s41467-018-04448-6.
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, Yan H. The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma. Nat Commun. 2018 May 25;9(1):2087.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

May 25, 2018

Volume

9

Issue

1

Start / End Page

2087

Location

England

Related Subject Headings

  • Young Adult
  • Telomere Homeostasis
  • Telomerase
  • Survival Analysis
  • Promoter Regions, Genetic
  • Mutation
  • Middle Aged
  • Male
  • Isocitrate Dehydrogenase
  • Humans