Mutation analysis of RAD51L1 (RAD51B/REC2) in multiple-case, non-BRCA1/2 breast cancer families

• Published in: Breast cancer research and treatment Vol. 129; no. 1; pp. 255 - 263
• Main Authors: Johnson, Julie, Healey, Sue, Khanna, Kum Kum, Chenevix-Trench, Georgia
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.08.2011; Springer; Springer Nature B.V
• Subjects: Alleles; Base Sequence; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Brief Report; Cancer research; DNA repair; DNA-Binding Proteins - genetics; Female; Gene Frequency - genetics; Genes; Genes, BRCA1; Genes, BRCA2; Genetic Predisposition to Disease; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Mutation; Mutation - genetics; Oncology; Polymorphism, Single Nucleotide - genetics; Tumors; Mutation screening; High resolution melt (HRM) analysis; Familial breast cancer; High resolution; Breast disease; Breast cancer; Malignant tumor; Medical screening; Mammary gland diseases; Screening; BRCA2 gene; Analysis; RAD51L1; Familial cancer; Genetics; Mutation; BRCA1 gene; Cancer
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-011-1539-6

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 double-strand 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 high-penetrance breast cancer susceptibility gene.