Skip to main content

Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas.

Publication ,  Journal Article
Killela, PJ; Pirozzi, CJ; Healy, P; Reitman, ZJ; Lipp, E; Rasheed, BA; Yang, R; Diplas, BH; Wang, Z; Greer, PK; Zhu, H; Wang, CY; Friedman, H ...
Published in: Oncotarget
March 30, 2014

Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or occur exclusively of one another in glioma subtypes presents a unique opportunity to guide glioma classification and prognosis. We analyzed the relationship between overall survival (OS) and the presence of IDH1/2 and TERT promoter mutations in a panel of 473 adult gliomas. We hypothesized and show that genetic signatures capable of distinguishing among several types of gliomas could be established providing clinically relevant information that can serve as an adjunct to histopathological diagnosis. We found that mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon in primary GBM. In oligodendrogliomas, TERT promoter and IDH1/2 mutations co-occurred in 79% of cases. Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months. Analyzing gliomas based on their genetic signatures allows for the stratification of these patients into distinct cohorts, with unique prognosis and survival.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

March 30, 2014

Volume

5

Issue

6

Start / End Page

1515 / 1525

Location

United States

Related Subject Headings

  • Telomerase
  • Survival Rate
  • Promoter Regions, Genetic
  • Prognosis
  • Neoplasm Grading
  • Mutation
  • Middle Aged
  • Male
  • Isocitrate Dehydrogenase
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Killela, P. J., Pirozzi, C. J., Healy, P., Reitman, Z. J., Lipp, E., Rasheed, B. A., … Bigner, D. D. (2014). Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. Oncotarget, 5(6), 1515–1525. https://doi.org/10.18632/oncotarget.1765
Killela, Patrick J., Christopher J. Pirozzi, Patrick Healy, Zachary J. Reitman, Eric Lipp, B Ahmed Rasheed, Rui Yang, et al. “Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas.Oncotarget 5, no. 6 (March 30, 2014): 1515–25. https://doi.org/10.18632/oncotarget.1765.
Killela PJ, Pirozzi CJ, Healy P, Reitman ZJ, Lipp E, Rasheed BA, et al. Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. Oncotarget. 2014 Mar 30;5(6):1515–25.
Killela, Patrick J., et al. “Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas.Oncotarget, vol. 5, no. 6, Mar. 2014, pp. 1515–25. Pubmed, doi:10.18632/oncotarget.1765.
Killela PJ, Pirozzi CJ, Healy P, Reitman ZJ, Lipp E, Rasheed BA, Yang R, Diplas BH, Wang Z, Greer PK, Zhu H, Wang CY, Carpenter AB, Friedman H, Friedman AH, Keir ST, He J, He Y, McLendon RE, Herndon JE, Yan H, Bigner DD. Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. Oncotarget. 2014 Mar 30;5(6):1515–1525.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

March 30, 2014

Volume

5

Issue

6

Start / End Page

1515 / 1525

Location

United States

Related Subject Headings

  • Telomerase
  • Survival Rate
  • Promoter Regions, Genetic
  • Prognosis
  • Neoplasm Grading
  • Mutation
  • Middle Aged
  • Male
  • Isocitrate Dehydrogenase
  • Humans