Distinct germ line polymorphisms underlie glioma morphologic heterogeneity

Robert B. Jenkins, Margaret R. Wrensch, Derek Johnson, Brooke L. Fridley, Paul A. Decker, Yuanyuan Xiao, Thomas M. Kollmeyer, Amanda L. Rynearson, Stephanie Fink, Terri Rice, Lucie S. McCoy, Chandralekha Halder, Matthew L. Kosel, Caterina Giannini, Tarik Tihan, Brian P. O'Neill, Daniel H. Lachance, Ping Yang, Joseph Wiemels, John K. Wiencke

Research output: Contribution to journalArticle

63 Scopus citations

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 casecontrol 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.

Original languageEnglish (US)
Pages (from-to)13-18
Number of pages6
JournalCancer Genetics
Volume204
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • 1p/19q deletion
  • Genetic association
  • Glioma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Jenkins, R. B., Wrensch, M. R., Johnson, D., Fridley, B. L., Decker, P. A., Xiao, Y., Kollmeyer, T. M., Rynearson, A. L., Fink, S., Rice, T., McCoy, L. S., Halder, C., Kosel, M. L., Giannini, C., Tihan, T., O'Neill, B. P., Lachance, D. H., Yang, P., Wiemels, J., & Wiencke, J. K. (2011). Distinct germ line polymorphisms underlie glioma morphologic heterogeneity. Cancer Genetics, 204(1), 13-18. https://doi.org/10.1016/j.cancergencyto.2010.10.002