ORPHA: 182067; MONDO: 0013095;
Cytogenetic location: 20q13.33 Genomic coordinates (GRCh38) : 20:59,700,001-64,444,167
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 20q13.33 | {Glioma susceptibility 6} | 613031 | 2 |
For a general phenotypic description and a discussion of genetic heterogeneity of glioma, see GLM1 (137800).
Working from the hypothesis that coinheritance of low-risk variants contributes to the 2-fold increased risk of glioma in relatives of individuals with primary brain tumors, Shete et al. (2009) conducted a metaanalysis of 2 glioma genomewide association studies by genotyping 550,000 tagged SNPs in a total of 1,878 cases and 3,670 controls, with validation in 3 additional independent series totaling 2,545 cases and 2,953 controls. They observed significant association of a single-nucleotide polymorphism (SNP), rs6010620 (OR = 1.28, 95% CI 1.21-1.35, P = 2.52 x 10(-12)) in intron 12 of the helicase gene RTEL1 (608833) and mapping within a 65-kb region of linkage disequilibrium on chromosome 20q13.33. Amplification of 20q13.33 was seen in approximately 30% of gliomas with copy number change correlating with RTEL1 expression. RTEL1 maintains genomic stability directly by suppressing homologous recombination.
Wrensch et al. (2009) conducted a principal component-adjusted genomewide association study of 275,895 autosomal variants among 692 adult high-grade glioma cases, 622 from the San Francisco Adult Glioma Study and 70 from the Cancer Genome Atlas, and 3,992 controls. The replication sample was performed in the 13 SNPs with a P value of less than 10(-6) using independent data from 176 high-grade glioma cases and 174 controls from the Mayo Clinic. They found significant association of 2 SNPs in the RTEL1 gene with high-grade glioma: rs6010620 (combined P = 3.4 x 10(-9)) and rs4809324 in intron 17 (combined P = 1.70 x 10(-9)).
Shete, S., Hosking, F. J., Robertson, L. B., Dobbins, S. E., Sanson, M., Malmer, B., Simon, M., Marie, Y., Boisselier, B., Delattre, J.-V., Hoang-Xuan, K., El Hallani, S., and 25 others. Genome-wide association study identifies five susceptibility loci for glioma. Nature Genet. 41: 899-904, 2009. [PubMed: 19578367] [Full Text: https://doi.org/10.1038/ng.407]
Wrensch, M., Jenkins, R. B., Chang, J. S., Yeh, R.-F., Xiao, Y., Decker, P. A., Ballman, K. V., Berger, M., Buckner, J. C., Chang, S., Giannini, C., Halder, C., and 16 others. Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nature Genet. 41: 905-908, 2009. [PubMed: 19578366] [Full Text: https://doi.org/10.1038/ng.408]