Madonna R Peter1,2, Misha Bilenky3, Ruth Isserlin4, Gary D Bader4, Shu Yi Shen5, Daniel D De Carvalho5,6, Aaron R Hansen7, Pingzhao Hu8, Neil E Fleshner9, Anthony M Joshua7,10, Martin Hirst3,11, Bharati Bapat1,2. 1. Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, M5G 1X5, Canada. 2. Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada. 3. Canada's Michael Smith Genome Science Centre, BC Cancer Agency, Vancouver, BC, V5Z 4S6, Canada. 4. Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada. 5. Princess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 2C1, Canada. 6. Department of Medical Biophysics, University of Toronto, Toronto, ON, M5G 1L7, Canada. 7. Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, ON, M5G 2C1, Canada. 8. Department of Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, MB, R3E 3N4, Canada. 9. Division of Urology, Department of Surgical Oncology, University Health Network, Toronto, ON, M5G 2C1, Canada. 10. Department of Medical Oncology, Kinghorn Cancer Centre, Darlinghurst, NSW 2010, Australia. 11. Department of Microbiology & Immunology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
Abstract
Aim: We examined methylation changes in cell-free DNA (cfDNA) in metastatic castration-resistant prostate cancer (mCRPC) during treatment. Patients & methods: Genome-wide methylation analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed. Results: Alterations in methylation states of genes previously implicated in prostate cancer progression were observed and patients that maintained methylation changes throughout therapy tended to have a longer time to clinical progression. Importantly, we also report that markers associated with a highly aggressive form of the disease, neuroendocrine-CRPC, were associated with a faster time to clinical progression. Conclusion: Our findings highlight the potential of monitoring the cfDNA methylome during therapy in mCRPC, which may serve as predictive markers of response to androgen-targeting agents.
Aim: We examined methylation changes in cell-free DNA (cfDNA) in metastatic castration-resistant prostate cancer (mCRPC) during treatment. Patients & methods: Genome-wide methylation analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed. Results: Alterations in methylation states of genes previously implicated in prostate cancer progression were observed and patients that maintained methylation changes throughout therapy tended to have a longer time to clinical progression. Importantly, we also report that markers associated with a highly aggressive form of the disease, neuroendocrine-CRPC, were associated with a faster time to clinical progression. Conclusion: Our findings highlight the potential of monitoring the cfDNA methylome during therapy in mCRPC, which may serve as predictive markers of response to androgen-targeting agents.
Entities:
Keywords:
DNA methylation; circulating cell free DNA; epigenetic modifications; genome-wide methylation analysis; metastatic castration-resistant prostate cancer
Authors: Megan E Barefoot; Netanel Loyfer; Amber J Kiliti; A Patrick McDeed; Tommy Kaplan; Anton Wellstein Journal: Front Genet Date: 2021-07-27 Impact factor: 4.772
Authors: Madonna R Peter; Misha Bilenky; Alastair Davies; Ruth Isserlin; Gary D Bader; Neil E Fleshner; Martin Hirst; Amina Zoubeidi; Bharati Bapat Journal: Sci Rep Date: 2021-03-23 Impact factor: 4.379