Low-Frequency Gene Variant Linked to Brain Tumors
(HealthDay News) – A low-frequency gene variant, rs55705857, is strongly associated with the risk of developing gliomas, with the strongest association seen in the presence of mutations in IDH1 and IDH2.
Robert B. Jenkins, MD, PhD, from the Mayo Clinic College of Medicine in Rochester, MN, and colleagues used tag single nucleotide polymorphism (SNP) array genotyping and imputation, together with long-range polymerase chain reaction and pooled next-generation sequencing, followed by validation custom genotyping in 1,657 glioma patients and 1,301 controls to identify SNPs at 8q24.21 associated with gliomas.
The researchers found that seven low-frequency SNPs were strongly associated with glioma risk. The most strongly associated SNP, rs55705857, which appeared to be a microRNA based on structural modeling, was most strongly associated with oligodendroglial tumors and gliomas with mutant IDH1 (odds ratio [OR], 5.1) or IDH2 (OR, 4.8). The variant was also strongly associated with grades 2–4 astrocytomas with mutant IDH1 or IDH2 (OR, 5.16–6.66). The variant was not associated with astrocytomas with wild-type IDH1 or IDH2.
"Our results strongly suggest that the glioma risk locus in the 8q24 (CCDC26) region identified in the present study might interact with IDH gene mutations and/or the downstream effects of such mutations to facilitate the development and progression of gliomas," Jenkins and colleagues conclude.