Genomic analysis of estrogen receptor-associated breast cancer
December 2016
University of Pittsburgh, Pittsburgh, USA(1)
University of Pittsburgh Cancer Institute, Pittsburgh, USA(2)
University of Pittsburgh Cancer Institute, Pittsburgh, USA(2)
Estrogen receptors are known to be critical for breast cancer through DNA binding mechanisms, leading to transcriptomic and phenotypic changes. Thus, single nucleotide variants in estrogen receptor binding sites might be involved in disease progression. Here, a computational analysis to identify single nucleotide variants in estrogen receptor binding sites is performed using chromatin immunoprecipitation sequencing data from different breast cancer models and further validated with human breast cancer cells to identify allele-specific binding. The analysis identified an intronic single nucleotide variant predicted to increase estrogen receptor binding and was experimentally validated. Furthermore, 17 regulatory single nucleotide variants correlated with expression of adjacent genes in estrogen receptor-associated breast cancer, from which GSTM1 promoter was the top candidate and showed to be correlated with higher expression of GSTM1 in estrogen receptor-associated tumors and better outcome in patients. Overall, the researchers establish a computational pipeline that can be used to investigate and elucidate key single nucleotide variants that can potentially regulate target genes contributing to the outcome of breast cancer in patients.
Non-coding single nucleotide variants affecting estrogen receptor binding and activity
Adrian V Lee(1), Steffi Oesterreich(2)
Added on: 10-12-2021
[1] https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-016-0382-0[2] https://data.jrc.ec.europa.eu/dataset/ffebe454-ed9a-47cf-8a33-8cf70c1b7d38
