Recent Research Highlights

RAD51D mutations cause Ovarian Cancer

Press Release

We and others have identified several DNA repair genes that predispose to breast and/or ovarian cancer. In this study we analysed RAD51D, a key member of DNA repair pathways, in 911 families with breast-ovarian cancer and 1060 population controls. We identified mutations that lead to premature protein truncation in 8 cases compared to only 1 control. The association was principally ovarian cancer; RAD51D mutations are associated with a 6 fold increased risk of the disease, which equates to a 10% lifetime risk of ovarian cancer. By contrast there was no significant increase in the risk of breast cancer. Our data indicate that RAD51D mutation testing may have clinical utility in individuals with ovarian cancer and their families. Moreover, we also show that cells deficient in RAD51D are sensitive to treatment with a PARP inhibitor, suggesting a possible therapeutic approach for cancers arising in RAD51D mutation carriers.

Nature Genetics: Published Online 7 August 2011

Average age-related cumulative risk of ovarian cancer in RAD51D mutation carriers, BRCA1 and BRCA2 mutation carriers22 and the general population

CEP57 mutations cause Aneuploidy

We used exome sequencing to analyse all protein-coding genes in a family with two boys with mosaic variegated aneuploidy, a rare disease characterised by multiple different constitutional aneuploidies together with mild features such as growth retardation and developmental delay. We identified loss-of-function CEP57 mutations in the boys and three additional cases. CEP57 is a centrosomal protein involved in nucleating and stabilizing microtubules. Our data indicates that these functions of CEP57 are crucial in maintaining correct chromosomal number during cell division.

Nature Genetics 2011 43(6):527-9

Screenshot of NextGENe sequence alignment viewer showing the CEP57 mutations