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. 2012 Oct;44(10):1122-5.
doi: 10.1038/ng.2388. Epub 2012 Aug 26.

A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation

Robert B Jenkins  1 , Yuanyuan Xiao, Hugues Sicotte, Paul A Decker, Thomas M Kollmeyer, Helen M Hansen, Matthew L Kosel, Shichun Zheng, Kyle M Walsh, Terri Rice, Paige Bracci, Lucie S McCoy, Ivan Smirnov, Joseph S Patoka, George Hsuang, Joe L Wiemels, Tarik Tihan, Alexander R Pico, Michael D Prados, Susan M Chang, Mitchel S Berger, Alissa A Caron, Stephanie R Fink, Chandralekha Halder, Amanda L Rynearson, Brooke L Fridley, Jan C Buckner, Brian P O'Neill, Caterina Giannini, Daniel H Lachance, John K Wiencke, Jeanette E Eckel-Passow, Margaret R Wrensch
Affiliations

A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation

Robert B Jenkins et al. Nat Genet. 2012 Oct.

Abstract

Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.21 that were strongly associated with glioma risk (P=1×10(-25) to 1×10(-14)). The most strongly associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six SNPs and two previously published SNPs. After stratifying by histological and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors and gliomas with mutant IDH1 or IDH2 (odds ratio (OR)=5.1, P=1.1×10(-31) and OR=4.8, P=6.6×10(-22), respectively). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2-4) (OR=5.16-6.66, P=4.7×10(-12) to 2.2×10(-8)) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P=0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA.

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Conflict of interest statement

Competing Financial Interests

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Case-control SNP associations with oligodendroglioma risk for 157 SNPs within the 8q24.21 (CCDC26) region by study site, Mayo Clinic (red) and University of California San Francisco (UCSF) (blue). The −log10 p-value of the association of each SNP versus chromosome 8q24 position is plotted. Only Stage 2 validation genotyping data are illustrated. The recombination rate for the region using HapMap is plotted in the lower part of the figure.
Figure 2
Figure 2
Glioma case-control odds ratios (ORs), 95% confidence intervals (CIs), and (−log10p) for SNPs within the 8q24.21 (CCDC26) region. A: Associations of all gliomas with 7 most strongly and significantly associated SNPs along with two SNPs from prior studies (1, 2) (rs4295627 and rs891835). B: Associations of rs55705857 G allele with various glioma morphologic subtypes. C: Association of rs55705857 G allele with glioma morphologic subtypes further stratified by presence or absence of tumor IDH1 or IDH2 mutation. Only Stage 2 validation genotyping data are illustrated. Abbreviations: MOA=mixed oligoastrocytoma, Oligo=oligodendroglioma, GBM=glioblastoma
See this image and copyright information in PMC

References

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