Mutation analysis of RAD51L1 (RAD51B/REC2) in multiple-case, non-BRCA1/2 breast cancer families
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Julie Johnson Sue Healey Kum Kum Khanna kConFab Georgia Chenevix-Trench
- چاپ و سال / کشور: 2011
Description
Although a significant proportion of familial aggregation of breast cancer remains unexplained, many of the currently known breast cancer susceptibility genes, including BRCA1, BRCA2 and TP53, play a role in maintaining genome integrity by engaging in DNA repair. RAD51L1 is one of the five RAD51 paralogs involved in homologous recombination (HR) repair of DNA doublestrand breaks (DSBs); it also interacts directly with p53. Deleterious mutations have been found in one RAD51 paralog, RAD51C (RAD51L2), in non-BRCA1/2 breast and ovarian cancer families, which suggests that all five paralogs are strong candidate breast cancer susceptibility genes. A genome-wide association study (GWAS) has already identified a single nucleotide polymorphism (SNP) deep within intron 10 of RAD51L1 as a risk locus for breast cancer. Based on its biological functions and association with RAD51C, there is reason to suggest that RAD51L1 (RAD51B/REC2) may also contain high risk mutations in the gene that give rise to multiple-case breast cancer families. In order to investigate this hypothesis, we have used high resolution melt (HRM) analysis to screen RAD51L1 for germline mutations in 188 non-BRCA1/2 multiple-case breast cancer families and 190 controls. We identified a total of seven variants: one synonymous, three intronic, and three previously identified SNPs, but no truncating or nonsense changes. Therefore, our results suggest that RAD51L1 is unlikely to represent a highpenetrance breast cancer susceptibility gene
Breast Cancer Res Treat (2011) 129:255–263 DOI 10.1007/s10549-011-1539-6 Received: 6 March 2011 / Accepted: 19 April 2011 / Published online: 28 April 2011
