TY - JOUR
T1 - Distinct germ line polymorphisms underlie glioma morphologic heterogeneity
AU - Jenkins, Robert B.
AU - Wrensch, Margaret R.
AU - Johnson, Derek
AU - Fridley, Brooke L.
AU - Decker, Paul A.
AU - Xiao, Yuanyuan
AU - Kollmeyer, Thomas M.
AU - Rynearson, Amanda L.
AU - Fink, Stephanie
AU - Rice, Terri
AU - McCoy, Lucie S.
AU - Halder, Chandralekha
AU - Kosel, Matthew L.
AU - Giannini, Caterina
AU - Tihan, Tarik
AU - O'Neill, Brian P.
AU - Lachance, Daniel H.
AU - Yang, Ping
AU - Wiemels, Joseph
AU - Wiencke, John K.
N1 - Funding Information:
The research at Mayo Clinic was funded by NIH grants P50 CA108961 (the Mayo Clinic Brain Tumor SPORE) and RC1 NS068222. Work at University of California, San Francisco was supported by NIH grants R01 CA52689 and UCSF Brain Tumor SPORE, P50CA097257, as well as by grants from the National Brain Tumor Foundation, the UCSF Lewis Chair in Brain Tumor Research and by donations from families and friends of John Berardi, Helen Glaser and Elvera Olsen. We thank the University of Georgia Genome Center and the Mayo Clinic Genotyping Core for performing the custom SNP analyses. In addition to C. Gianinni, we thank B. Scheithauer for his careful histological review of all the gliomas collected at the Mayo Clinic. The San Francisco Adult Glioma Study thanks the Northern California Cancer Center for glioma patient case finding; we also thank Kenneth Aldape for pathology review and the pathology departments of Alexian, Alta Bates, Brookside, California Pacific, Drs. Pinole, Eden, El Camino, Good Samaritan, Highland, John Muir, Kaiser Redwood City, Kaiser San Francisco, Kaiser Santa Teresa, Los Gatos, Los Medanos, Marin General, Merrithew, Mills Peninsula, Mt. Diablo Hospital, Mt. Zion, Naval Hospital, O’Connor, Ralph K. Davies, Saint Louise, San Francisco General, San Jose, San Leandro, San Mateo County, San Ramon Valley, Santa Clara Valley, Sequoia, Seton, St. Francis, St. Luke’s, St. Rose, Stanford, Summit, UC San Francisco, Valley Livermore, Veterans Palo Alto, Veterans SF, and Washington Hospitals and Medical Centers for providing tumor specimens for review. We used HapMap data to generate the recombination frequencies surrounding the associated 8q24 region. We thank the International HapMap Consortium (23) , and we thank the people in the Utah CEPH community, who allowed the samples they donated earlier to be used by the International HapMap Consortium.
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - 1p/19q deletion
KW - Genetic association
KW - Glioma
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U2 - 10.1016/j.cancergencyto.2010.10.002
DO - 10.1016/j.cancergencyto.2010.10.002
M3 - Article
C2 - 21356187
AN - SCOPUS:79955664968
SN - 2210-7762
VL - 204
SP - 13
EP - 18
JO - Cancer Genetics
JF - Cancer Genetics
IS - 1
ER -