Heritable DNA methylation marks associated with familial breast and prostate cancer

Mahnaz Hosseinpour
PhD student
University of Melbourne

PhD completion seminar

Breast cancer and prostate cancer are the most prevalent cancers among women and men and the second leading cancer-associated death among males and females in Australia respectively. The familial aggregation of breast and prostate cancer have been illustrated in several epidemiological studies. Some families have multiple cases of both breast and prostate cancer. However, germline mutations in high-risk genes such as BRCA1 and BRCA2 account for only a small fraction of this familial risk. DNA methylation can mimic the effects of genetic mutations and in some instances DNA methylation is heritable. Recent studies demonstrate that some DNA methylation marks are associated with increased cancer risk. However, it is not clear how changes in DNA methylation mediate phenotypes that result in increased cancer risk.

This study applied genome-wide methylation measures to multiple-case breast and prostate cancer families and identified 1,000 heritable DNA methylation marks. A CRISPR based strategy was developed to edit DNA methylation and perform a systematic high throughput pooled screen for heritable DNA methylation sites that mediate breast cancer related phenotypes such as proliferation and DNA damage. This study provides new opportunities for the development / repurposing of epigenetic therapeutics targeting these heritable DNA methylation marks associated with increased cancer risk.

Mahnaz Hosseinpour is a PhD student in the field of cancer epigenetics. She completed her B.SC and M.SC in medical biotechnology at the University of Putra Malaysia. She started her PhD in 2017. Her research aims are to identify epigenetic cancer risk factors with defined phenotypes in breast cancer and prostate cancer, and to ultimately provide strategies for early detection and targeted therapies.