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Approved research

Establishing the biological importance of germline variants in SMARCA4

Principal Investigator: Dr William Foulkes
Approved Research ID: 57060
Approval date: April 3rd 2020

Lay summary

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but very aggressive type of ovarian tumour that affects young women. Tumors are almost always caused by mutations in the gene SMARCA4, and these mutations are often inherited. It is now possible to screen for mutations in families using the latest sequencing technologies as part of clinical care. Many genetic variations have been observed as a result of such screening, but it is not always clear whether the genetic changes observed are mutations that would increase the risk for the disease or simple genetic variations that will have no impact on health. The project proposed here will use a combination of clinical & theoretical genetics and functional, lab-based experiments to classify variants of unknown significance. In the process, we will also streamline a pipeline that can be used to classify other variants observed in the future. This work will improve the efficacy of genetic testing for patients, will aid in determining who is at risk for SCCOHT and will reduce the number of unnecessary preventive oophorectomies.