Germline alterations in the CLSPN gene in breast cancer families.

About 5-10% of breast cancer is thought to be due to an inherited disease predisposition. Currently known genes account for less than half of the hereditary cases. Claspin, a tumor suppressor protein encoded by the CLSPN gene, is involved in monitoring of replication and sensoring of DNA damage and cooperates with CHK1 and BRCA1. Association with certain cell proliferation stimulatory features has also been described. Many previously identified susceptibility factors act in similar functional pathways as claspin, suggesting possible involvement of CLSPN in heritable breast cancer susceptibility. Here we have screened affected index cases from 125 Finnish cancer families for germline defects in CLSPN using conformation sensitive gel electrophoresis (CSGE) and direct sequencing. Altogether seven different sequence changes were observed, but none of them appeared to associate with breast cancer susceptibility. To our knowledge, this is the first study reporting the mutation screening of the CLSPN gene in familial breast cancer cases.