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Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.

Publication ,  Journal Article
Eckel-Passow, JE; Lachance, DH; Molinaro, AM; Walsh, KM; Decker, PA; Sicotte, H; Pekmezci, M; Rice, T; Kosel, ML; Smirnov, IV; Sarkar, G ...
Published in: N Engl J Med
June 25, 2015

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.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

June 25, 2015

Volume

372

Issue

26

Start / End Page

2499 / 2508

Location

United States

Related Subject Headings

  • Telomerase
  • Proportional Hazards Models
  • Promoter Regions, Genetic
  • Neoplasm Grading
  • Mutation
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Isocitrate Dehydrogenase
  • Humans
 

Citation

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Eckel-Passow, J. E., Lachance, D. H., Molinaro, A. M., Walsh, K. M., Decker, P. A., Sicotte, H., … Jenkins, R. B. (2015). Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med, 372(26), 2499–2508. https://doi.org/10.1056/NEJMoa1407279
Eckel-Passow, Jeanette E., Daniel H. Lachance, Annette M. Molinaro, Kyle M. Walsh, Paul A. Decker, Hugues Sicotte, Melike Pekmezci, et al. “Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.N Engl J Med 372, no. 26 (June 25, 2015): 2499–2508. https://doi.org/10.1056/NEJMoa1407279.
Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, et al. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med. 2015 Jun 25;372(26):2499–508.
Eckel-Passow, Jeanette E., et al. “Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.N Engl J Med, vol. 372, no. 26, June 2015, pp. 2499–508. Pubmed, doi:10.1056/NEJMoa1407279.
Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, Pekmezci M, Rice T, Kosel ML, Smirnov IV, Sarkar G, Caron AA, Kollmeyer TM, Praska CE, Chada AR, Halder C, Hansen HM, McCoy LS, Bracci PM, Marshall R, Zheng S, Reis GF, Pico AR, O’Neill BP, Buckner JC, Giannini C, Huse JT, Perry A, Tihan T, Berger MS, Chang SM, Prados MD, Wiemels J, Wiencke JK, Wrensch MR, Jenkins RB. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med. 2015 Jun 25;372(26):2499–2508.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

June 25, 2015

Volume

372

Issue

26

Start / End Page

2499 / 2508

Location

United States

Related Subject Headings

  • Telomerase
  • Proportional Hazards Models
  • Promoter Regions, Genetic
  • Neoplasm Grading
  • Mutation
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Isocitrate Dehydrogenase
  • Humans