title: Distinct germ line polymorphisms underlie glioma morphologic heterogeneity.
abstract: Two recent genome-wide association studies reported that single nucleotide polymorphisms (SNPs) in (or near) TERT (5p15), CCDC26 (8q24), CDKN2A/B (9p21), PHLDB1 (11q23), and RTEL1 (20q13) are associated with infiltrating glioma. From these reports, it was not clear whether the single nucleotide polymorphism associations predispose to glioma in general or whether they are specific to certain glioma grades or morphologic subtypes. To identify hypothesized associations between susceptibility loci and tumor subtype, we genotyped two case-control groups composed of the spectrum of infiltrating glioma subtypes and stratified the analyses by type. We report that specific germ line polymorphisms are associated with different glioma subtypes. CCDC26 (8q24) region polymorphisms are strongly associated with oligodendroglial tumor risk (rs4295627, odds ratio [OR] = 2.05, P = 8.3 × 10(-11)) but not glioblastoma risk. The opposite is true of RTEL (20q13) region polymorphisms, which are significantly associated with glioblastoma (rs2297440, OR = 0.56, P = 4.6 × 10(-10)) but not oligodendroglial tumor. The SNPs in or near CCDC26 (8q24) are associated with oligodendroglial tumors regardless of combined 1p and 19q deletion status; however, the association is greatest for those with combined deletion (rs4295627, OR = 2.77, P = 2.6 × 10(-9)). These observations generate hypotheses concerning the possible mechanisms by which specific SNPs (or alterations in linkage disequilibrium with such SNPs) are associated with glioma development.
authors.affiliation: Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA. rjenkins@mayo.edu
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wrensch
authors.forename: Derek
authors.initials: D
authors.lastname: Johnson
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kollmeyer
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Rynearson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fink
authors.forename: Terri
authors.initials: T
authors.lastname: Rice
authors.forename: Lucie S
authors.initials: LS
authors.lastname: McCoy
authors.forename: Chandralekha
authors.initials: C
authors.lastname: Halder
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Kosel
authors.forename: Caterina
authors.initials: C
authors.lastname: Giannini
authors.forename: Tarik
authors.initials: T
authors.lastname: Tihan
authors.forename: Brian P
authors.initials: BP
authors.lastname: O'Neill
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lachance
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Joseph
authors.initials: J
authors.lastname: Wiemels
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
mesh_terms: D000328:Adult; D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic