A HRM-based screening method detects RAD51C germ-line deleterious mutations in Spanish breast and ovarian cancer families

作者：Romero Atocha; Perez Segura Pedro; Tosar Alicia; Angel Garcia Saenz Josd; Diaz Rubio Eduardo; Caldes Trinidad^*; de la Hoya Miguel

来源：Breast Cancer Research and Treatment, 2011, 129(3): 939-946.

DOI：10.1007/s10549-011-1543-x

• RAD51C
• HRM
• Hereditary breast and ovarian cancer
• Germ-line mutation

The RAD51C gene has been recently proposed as a high-penetrance breast and ovarian cancer gene. However, early replication studies have failed to confirm the finding. Thus, further studies in larger cohorts should be conducted in order to clarify the role of RAD51C as a cancer susceptibility gene. Here, we describe a high-resolution melting analysis (HRMA)-based method developed for presequence screening of RAD51C sequence variants. We have screened RAD51C sequence variants by HRMA in 492 breast cancer patients with family history of breast and/or ovarian cancer that were previously tested negative for BRCA1/2. All variants were confirmed by direct sequencing. We have detected 12 different RAD51C germ-line sequence variants, including eight transitions, two transversion, and two indels (insA, and delT). All these variants generated melting profiles which differ from wild type homozygous controls. Interestingly, we have identified one clearly pathogenic mutation (c.774delT) in the subset of 101 breast and ovarian cancer families, supporting that RAD51C is a human breast and ovarian cancer susceptibility gene.

• 出版日期2011-10