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.).
authors.affiliation: From the Departments of Health Sciences Research (J.E.E.-P., P.A.D., H.S., M.L.K.), Laboratory Medicine and Pathology (D.H.L., G.S., A.A.C., T.M.K., C.E.P., A.R.C., C.H., C.G., R.B.J.), Neurology (D.H.L., B.P.O.), and Oncology (J.C.B.), Mayo Clinic, Rochester, MN; the Departments of Neurological Surgery (A.M.M., K.M.W., T.R., I.V.S., H.M.H., L.S.M., S.Z., A.P., M.S.B., S.M.C., M.D.P., J.K.W., M.R.W.), Epidemiology and Biostatistics (A.M.M., P.M.B., J.W., J.K.W., M.R.W.) and Pathology (M.P., R.M., G.F.R., A.P., T.T.) and the Institute of Human Genetics (J.W., J.K.W., M.R.W.), University of California, San Francisco, and the Bioinformatics Core, Gladstone Institutes (A.R.P.) - all in San Francisco; and the Department of Pathology and Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York (J.T.H.).
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Eckel-Passow
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lachance
authors.forename: Annette M
authors.initials: AM
authors.lastname: Molinaro
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Walsh
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.forename: Hugues
authors.initials: H
authors.lastname: Sicotte
authors.forename: Melike
authors.initials: M
authors.lastname: Pekmezci
authors.forename: Terri
authors.initials: T
authors.lastname: Rice
authors.forename: Matt L
authors.initials: ML
authors.lastname: Kosel
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Smirnov
authors.forename: Gobinda
authors.initials: G
authors.lastname: Sarkar
authors.forename: Alissa A
authors.initials: AA
authors.lastname: Caron
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kollmeyer
authors.forename: Corinne E
authors.initials: CE
authors.lastname: Praska
authors.forename: Anisha R
authors.initials: AR
authors.lastname: Chada
authors.forename: Chandralekha
authors.initials: C
authors.lastname: Halder
authors.forename: Helen M
authors.initials: HM
authors.lastname: Hansen
authors.forename: Lucie S
authors.initials: LS
authors.lastname: McCoy
authors.forename: Paige M
authors.initials: PM
authors.lastname: Bracci
authors.forename: Roxanne
authors.initials: R
authors.lastname: Marshall
authors.forename: Shichun
authors.initials: S
authors.lastname: Zheng
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Reis
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Pico
authors.forename: Brian P
authors.initials: BP
authors.lastname: O'Neill
authors.forename: Jan C
authors.initials: JC
authors.lastname: Buckner
authors.forename: Caterina
authors.initials: C
authors.lastname: Giannini
authors.forename: Jason T
authors.initials: JT
authors.lastname: Huse
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
authors.forename: Tarik
authors.initials: T
authors.lastname: Tihan
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Berger
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Prados
authors.forename: Joseph
authors.initials: J
authors.lastname: Wiemels
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wrensch
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
mesh_terms: D000328:Adult; D017668:Age of Onset; D014408:Biomarkers, Tumor; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D018095:Germ-Line Mutation; D005910:Glioma / Q000145:classification / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D019098:Telomerase / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C509186:TERT protein, human; D019098:Telomerase