Genome-wide identification of chromosomal translocations induced by estradiol in breast cancer
Focal copy-number amplification is an oncogenic event in many cancers. Although several studies showed the complex structure of amplified oncogens and the evolution of amplicons after their formation, the origin of the initial amplicons remains poorly understood. To understand the mechanisms, we generated genome-wide chromosomal translocation maps with/out beta-estradiol in estrogen receptor (ER) positive breast cancer cells when a DNA double strand breark occurs in SHANK2 or RARA. We found that estrogen treatment induces DNA double strand breaks in the estrogen receptor target regions that are repaired by translocations, suggesting the role of estrogen in generating the original translocations initiating amplication. Overall design: We applied high-throughput genome-wide chromosomal translocation sequencing (HTGTS) to compare translocation patternes with/out estradiol treatment in MCF7 and T-47D breast cancer cells with DNA double strand breaks in either SHANK2 or RARA.