An Analysis of the Features and Dynamics of BRCA1 Promoter Methylation in Triple Negative Breast and Ovarian cancer
In: Student Reports, Summer 2021, The Jackson Laboratory
Francesca Menghi, Ph.D. and Edison Liu, MD
Triple-negative breast cancer (TNBC) and Ovarian Carcinomas with BRCA1 inactivating mutations (BRCA1mut) are sensitive to platinum-based therapies. Hypermethylation of the BRCA1 promoter (BRCA1meth) also disrupts BRCA1 activity but doesn’t seem to induce the same sensitivity to platinum-based therapies. This is likely due to the rapid demethylation of the BRCA1 promoter following exposure to anti-cancer therapies, which leads to restoration of BRCA1 function and the consequent development of resistance. To elucidate potential epigenetic and transcriptional changes associated with BRCA1 hypermethylation as well as BRCA1 demethylation following platinum-based therapies, this study analyzed differential methylation and gene expression between BRCA1meth and BRCA1nonmeth tumors in TNBC and Ovarian Cancer datasets. Methylation differences associated with the BRCA1 promoter appear to be focalized to the BRCA1 promoter locus, not related with genome-wide epigenetic changes.
Zhu, Angela, "An Analysis of the Features and Dynamics of BRCA1 Promoter
Methylation in Triple Negative Breast and Ovarian cancer" (2021). Summer and Academic Year Student Reports. 2687.