Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors Journal Article

Authors: Eckel-Passow, J. E.; Lachance, D. H.; Molinaro, A. M.; Walsh, K. M.; Decker, P. A.; Sicotte, H.; Pekmezci, M.; Rice, T.; Kosel, M. L.; Smirnov, I. V.; Sarkar, G.; Caron, A. A.; Kollmeyer, T. M.; Praska, C. E.; Chada, A. R.; Halder, C.; Hansen, H. M.; McCoy, L. S.; Bracci, P. M.; Marshall, R.; Zheng, S.; Reis, G. F.; Pico, A. R.; O'Neill, B. P.; Buckner, J. C.; Giannini, C.; Huse, J. T.; Perry, A.; Tihan, T.; Berger, M. S.; Chang, S. M.; Prados, M. D.; Wiemels, J.; Wiencke, J. K.; Wrensch, M. R.; Jenkins, R. B.
Article Title: Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors
Abstract: BACKGROUND The prediction of clinical behavior, response to therapy, and outcome of infiltrative glioma is challenging. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). We tested the hypothesis that within groups based on these features, tumors would have similar clinical variables, acquired somatic alterations, and germline variants. METHODS We scored tumors as negative or positive for each of these markers in 1087 gliomas and compared acquired alterations and patient characteristics among the five primary molecular groups. Using 11,590 controls, we assessed associations between these groups and known glioma germline variants. RESULTS Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. The mean age at diagnosis was lowest (37 years) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients who had gliomas with only TERT mutations. The molecular groups were independently associated with overall survival among patients with grade II or III gliomas but not among patients with grade IV gliomas. The molecular groups were associated with specific germline variants. CONCLUSIONS Gliomas were classified into five principal groups on the basis of three tumor markers. The groups had different ages at onset, overall survival, and associations with germline variants, which implies that they are characterized by distinct mechanisms of pathogenesis. (Funded by the National Institutes of Health and others.) Copyright © 2015 Massachusetts Medical Society.
Keywords: adult; cancer survival; controlled study; middle aged; gene mutation; major clinical study; overall survival; promoter region; glioma; cancer grading; genetic association; genetic variability; germ line; telomerase reverse transcriptase; onset age; marker gene; chromosome 1p; isocitrate dehydrogenase; chromosome 19q; tert gene; human; male; female; priority journal; article; idh gene
Journal Title: New England Journal of Medicine
Volume: 372
Issue: 26
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2015-06-25
Start Page: 2499
End Page: 2508
Language: English
DOI: 10.1056/NEJMoa1407279
PROVIDER: scopus
PMCID: PMC4489704
PUBMED: 26061753
Notes: Export Date: 3 August 2015 -- Source: Scopus
Citation Impact
MSK Authors
  1. Jason T Huse
    132 Huse