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

Jeanette E Eckel-Passow, Daniel H Lachance, Annette M. Molinaro, Kyle M. Walsh, Paul A. Decker, Hugues Sicotte, Melike Pekmezci, Terri Rice, Matt L. Kosel, Ivan V. Smirnov, Gobinda Sarkar, Alissa A. Caron, Thomas M. Kollmeyer, Corinne E. Praska, Anisha R. Chada, Chandralekha Halder, Helen M. Hansen, Lucie S. McCoy, Paige M. Bracci, Roxanne MarshallShichun Zheng, Gerald F. Reis, Alexander R. Pico, Brian Patrick O'Neill, Jan Craig Buckner, Caterina Giannini, Jason T. Huse, Arie Perry, Tarik Tihan, Mitchell S. Berger, Susan M. Chang, Michael D. Prados, Joseph Wiemels, John K. Wiencke, Margaret R. Wrensch, Robert Brian Jenkins

Research output: Contribution to journalArticle

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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.)

Original languageEnglish (US)
Pages (from-to)2499-2508
Number of pages10
JournalNew England Journal of Medicine
Volume372
Issue number26
DOIs
StatePublished - Jun 25 2015

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Glioma
Mutation
Neoplasms
Survival
National Institutes of Health (U.S.)
Tumor Biomarkers
Age of Onset
Chromosomes

ASJC Scopus subject areas

  • Medicine(all)

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Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. / Eckel-Passow, Jeanette E; Lachance, Daniel H; Molinaro, Annette M.; Walsh, Kyle M.; Decker, Paul A.; Sicotte, Hugues; Pekmezci, Melike; Rice, Terri; Kosel, Matt L.; Smirnov, Ivan V.; Sarkar, Gobinda; Caron, Alissa A.; Kollmeyer, Thomas M.; Praska, Corinne E.; Chada, Anisha R.; Halder, Chandralekha; Hansen, Helen M.; McCoy, Lucie S.; Bracci, Paige M.; Marshall, Roxanne; Zheng, Shichun; Reis, Gerald F.; Pico, Alexander R.; O'Neill, Brian Patrick; Buckner, Jan Craig; Giannini, Caterina; Huse, Jason T.; Perry, Arie; Tihan, Tarik; Berger, Mitchell S.; Chang, Susan M.; Prados, Michael D.; Wiemels, Joseph; Wiencke, John K.; Wrensch, Margaret R.; Jenkins, Robert Brian.

In: New England Journal of Medicine, Vol. 372, No. 26, 25.06.2015, p. 2499-2508.

Research output: Contribution to journalArticle

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 2015, 'Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors', New England Journal of Medicine, vol. 372, no. 26, pp. 2499-2508. https://doi.org/10.1056/NEJMoa1407279
Eckel-Passow, Jeanette E ; Lachance, Daniel H ; Molinaro, Annette M. ; Walsh, Kyle M. ; Decker, Paul A. ; Sicotte, Hugues ; Pekmezci, Melike ; Rice, Terri ; Kosel, Matt L. ; Smirnov, Ivan V. ; Sarkar, Gobinda ; Caron, Alissa A. ; Kollmeyer, Thomas M. ; Praska, Corinne E. ; Chada, Anisha R. ; Halder, Chandralekha ; Hansen, Helen M. ; McCoy, Lucie S. ; Bracci, Paige M. ; Marshall, Roxanne ; Zheng, Shichun ; Reis, Gerald F. ; Pico, Alexander R. ; O'Neill, Brian Patrick ; Buckner, Jan Craig ; Giannini, Caterina ; Huse, Jason T. ; Perry, Arie ; Tihan, Tarik ; Berger, Mitchell S. ; Chang, Susan M. ; Prados, Michael D. ; Wiemels, Joseph ; Wiencke, John K. ; Wrensch, Margaret R. ; Jenkins, Robert Brian. / Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. In: New England Journal of Medicine. 2015 ; Vol. 372, No. 26. pp. 2499-2508.
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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.)",
author = "Eckel-Passow, {Jeanette E} and Lachance, {Daniel H} and Molinaro, {Annette M.} and Walsh, {Kyle M.} and Decker, {Paul A.} and Hugues Sicotte and Melike Pekmezci and Terri Rice and Kosel, {Matt L.} and Smirnov, {Ivan V.} and Gobinda Sarkar and Caron, {Alissa A.} and Kollmeyer, {Thomas M.} and Praska, {Corinne E.} and Chada, {Anisha R.} and Chandralekha Halder and Hansen, {Helen M.} and McCoy, {Lucie S.} and Bracci, {Paige M.} and Roxanne Marshall and Shichun Zheng and Reis, {Gerald F.} and Pico, {Alexander R.} and O'Neill, {Brian Patrick} and Buckner, {Jan Craig} and Caterina Giannini and Huse, {Jason T.} and Arie Perry and Tarik Tihan and Berger, {Mitchell S.} and Chang, {Susan M.} and Prados, {Michael D.} and Joseph Wiemels and Wiencke, {John K.} and Wrensch, {Margaret R.} and Jenkins, {Robert Brian}",
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TY - JOUR

T1 - Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors

AU - Eckel-Passow, Jeanette E

AU - Lachance, Daniel H

AU - Molinaro, Annette M.

AU - Walsh, Kyle M.

AU - Decker, Paul A.

AU - Sicotte, Hugues

AU - Pekmezci, Melike

AU - Rice, Terri

AU - Kosel, Matt L.

AU - Smirnov, Ivan V.

AU - Sarkar, Gobinda

AU - Caron, Alissa A.

AU - Kollmeyer, Thomas M.

AU - Praska, Corinne E.

AU - Chada, Anisha R.

AU - Halder, Chandralekha

AU - Hansen, Helen M.

AU - McCoy, Lucie S.

AU - Bracci, Paige M.

AU - Marshall, Roxanne

AU - Zheng, Shichun

AU - Reis, Gerald F.

AU - Pico, Alexander R.

AU - O'Neill, Brian Patrick

AU - Buckner, Jan Craig

AU - Giannini, Caterina

AU - Huse, Jason T.

AU - Perry, Arie

AU - Tihan, Tarik

AU - Berger, Mitchell S.

AU - Chang, Susan M.

AU - Prados, Michael D.

AU - Wiemels, Joseph

AU - Wiencke, John K.

AU - Wrensch, Margaret R.

AU - Jenkins, Robert Brian

PY - 2015/6/25

Y1 - 2015/6/25

N2 - 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.)

AB - 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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DO - 10.1056/NEJMoa1407279

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JF - New England Journal of Medicine

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