RAD51C as a human cancer susceptibility gene

The present invention provides a novel susceptibility gene for hereditary cancers. RAD51C, which encodes for a protein involved in DNA repair, has been found to be mutated in families with breast and ovarian cancer, but not in healthy control subjects. In addition, the patients were all selected from pedigrees negative for mutations of BRCA1 and BRCA2 to particularly identify genetic mutations causing a cancer predisposition independently of already known determinants. All analyzed mutations were identified as mono-allelic germline mutations. Besides gynecological cancers, mutations of RAD51C were also detected in patients suffering from head and neck squamous cell carcinomas (HNSSC). Thus, the presence of mutations in RAD51C is associated with an increased predisposition of developing cancer and positions RAD51C as a high-risk cancer susceptibility gene. Furthermore, an abnormal RAD51C gene status correlates with an increased probability for response to a DNA-damaging therapeutic agent and therefore represents an ideal companion diagnostic.

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