Germline RAD51C mutations in ovarian cancer susceptibility

Area of Science:

• Genetics and Genomics
• Cancer Biology
• Molecular Oncology

Background:

• Fanconi anemia pathway genes, like BRCA2, PALB2, and BRIP1, are linked to hereditary breast cancer (BC) and ovarian cancer (OC) susceptibility.
• RAD51C, crucial for DNA double-strand break repair, has been implicated in Fanconi anemia-like disorders and potentially BC/OC predisposition.
• Previous studies reported conflicting results regarding RAD51C's role in BC/OC risk.

Purpose of the Study:

• To investigate the association between germline RAD51C mutations and increased risk of BC/OC.
• To determine the frequency of pathogenic RAD51C mutations in BRCA1/2-negative familial BC/OC cases.

Main Methods:

• Sanger sequencing of the RAD51C coding sequence was performed.
• 117 index cases from French or European families with a history of BC/OC and negative for BRCA1/2 mutations were screened.

Main Results:

• Three pathogenic RAD51C mutations were identified in 117 screened families.
• This represents a mutation frequency of 2.6% in the studied cohort.
• The findings support RAD51C as a BC/OC susceptibility gene.

Conclusions:

• RAD51C germline mutations are associated with an increased risk of developing BC/OC.
• RAD51C screening should be considered for families with multiple BC/OC cases, particularly those negative for BRCA1/2 mutations.