3D structure of DNA is 'rewired' in hormone-resistant ER+ breast cancers

3D structure of DNA is 'rewired' in hormone-resistant ER+ breast cancers

Study demonstrates accuracy of AI system in diagnosing prostate cancer Using chromosome conformation capture, a cutting-edge technique that provides a snapshot of how DNA is arranged and interacts in three dimensions in the cell, the researchers compared different ER+ breast cancer cells that were either sensitive or resistant to hormone treatment. "Between breast cancer cells that were still sensitive to hormone treatment and those that had developed resistance, we saw significant changes in 3D interactions of DNA regions that control gene activation. Including at genes that control the estrogen receptor levels in the cells," says Dr Achinger-Kawecka. "Further, we found that this 3D 'rewiring' occurred at DNA regions that were methylated, which is an epigenetic change that the team has already linked to hormone resistance." The researchers say that the altered DNA methylation at critical regulatory regions may explain how the 3D structure of DNA is rewired as a cancer cell develops hormone resistance, allowing the cancer to better evade treatment. A new path for breast cancer treatment "Cancer cells are always trying to outsmart therapy and it only takes one cell to evolve a different way to bypass a drug to cause a relapse in cancer," says Professor Clark. "Our study shows us just how much impact a change in the epigenome can have on cancer cell behavior." The researchers say the next step is to investigate whether epigenetic changes could be reversed to stop hormone resistance, using existing drugs that are already in clinical trials for other cancers, including lung and colorectal cancer. "Once ER+ breast cancer patients become resistant to hormone therapy, it is more difficult to treat," says Professor Clark. "We hope our research will help lead to combination treatments that allow women to take hormone therapy for longer, giving them better clinical outcomes." Source: Garvan Institute of Medical Research Journal reference: Achinger-Kawecka, J., et al. (2020) Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer. Nature Communications . doi.org/10.1038/s41467-019-14098-x .



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