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Two studies reveal the genetic reasons behind aggressive prostate cancer.
Posted On: January 13, 2017
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The Movember campaign (represented above with mustaches) supports men’s health, including prostate cancer research on ways of using a patient’s genetics to individualize treatment.
Prostate cancer is the most common cancer in men. Despite conventional treatments like radiation therapy and surgery, a significant proportion of men with cancer that is confined to the prostate gland will eventually develop aggressive disease that spreads to other organs. Two new studies by PM Senior Scientist Dr. Robert Bristow and his research team shed new light on the genetic reasons behind this switch.
The first study, performed in collaboration with Dr. Paul Boutros (Ontario Institute for Cancer Research), examined the genetic landscape of tumours in men with non-inherited prostate cancer. Using state-of-the-art DNA sequencing techniques and advanced computational analyses, the team found a genetic fingerprint that identifies which cancers are likely to become aggressive. This genetic fingerprint could be used as a test to identify those who would respond well to conventional treatments and those with disease that has already started to spread. The test outperforms traditional methods of distinguishing these groups.
The second study, performed in collaboration with Dr. Boutros and Dr. Gail Risbridger (Monash University), focused on a group of men with an inherited form of the disease known as BRCA2-associated prostate cancer. The research team analyzed the genetic profiles of these tumours and found that certain pathways involved in cell growth were abnormally regulated. These abnormalities are similar to those typically found in non-inherited prostate cancer tumours that are resistant to therapy and that spread through the body. As such, the BRCA2-associated tumours are already aggressive even before treatment, suggesting that therapies to offset this aggressiveness should be considered earlier.
"This is an exciting time in prostate cancer research in which the genetics of individual men and their cancers are beginning to dictate precise and customized treatment," says Dr. Bristow. "These studies are examples of how international collaboration and team science can crack the genetic code of tumours."
You can watch Dr. Bristow discusses his research in this video.
These works were supported by the Movember Foundation, Prostate Cancer Canada, the Ontario Institute for Cancer Research (through the Government of Ontario), the Princess Margaret Hospital Radiation Medicine Program, the Canadian Cancer Society Research Institute Scientist Award, the Terry Fox Research Institute, the Canadian Institutes of Health Research, Genome Canada, the Natural Sciences and Engineering Research Council of Canada, the National Health and Medical Research Council of Australia, the Victorian State Government Cancer Agency, TissuPath, the Prostate Cancer Foundation of Australia, the National Breast Cancer Foundation, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, the Cancer Foundation of Western Australia and The Princess Margaret Cancer Foundation.
Fraser M, Sabelnykova VY, Yamaguchi TN, Heisler LE, Livingstone J, Huang V, Shiah YJ, Yousif F, Lin X, Masella AP, Fox NS, Xie M, Prokopec SD, Berlin A, Lalonde E, Ahmed M, Trudel D, Luo X, Beck TA, Meng A, Zhang J, D'Costa A, Denroche RE, Kong H, Espiritu SM, Chua ML, Wong A, Chong T, Sam M, Johns J, Timms L, Buchner NB, Orain M, Picard V, Hovington H, Murison A, Kron K, Harding NJ, P'ng C, Houlahan KE, Chu KC, Lo B, Nguyen F, Li CH, Sun RX, de Borja R, Cooper CI, Hopkins JF, Govind SK, Fung C, Waggott D, Green J, Haider S, Chan-Seng-Yue MA, Jung E, Wang Z, Bergeron A, Pra AD, Lacombe L, Collins CC, Sahinalp C, Lupien M, Fleshner NE, He HH, Fradet Y, Tetu B, van der Kwast T, McPherson JD, Bristow RG, Boutros PC. Genomic hallmarks of localized, non-indolent prostate cancer. Nature. 2017 Jan 9. doi: 10.1038/nature20788.
Taylor RA, Fraser M, Livingstone J, Espiritu SM, Thorne H, Huang V, Lo W, Shiah YJ, Yamaguchi TN, Sliwinski A, Horsburgh S, Meng A, Heisler LE, Yu N, Yousif F, Papargiris M, Lawrence MG, Timms L, Murphy DG, Frydenberg M, Hopkins JF, Bolton D, Clouston D, McPherson JD, van der Kwast T, Boutros PC, Risbridger GP, Bristow RG. Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories. Nature Communications. 2017 Jan 9. doi: 10.1038/ncomms13671.
The first study, performed in collaboration with Dr. Paul Boutros (Ontario Institute for Cancer Research), examined the genetic landscape of tumours in men with non-inherited prostate cancer. Using state-of-the-art DNA sequencing techniques and advanced computational analyses, the team found a genetic fingerprint that identifies which cancers are likely to become aggressive. This genetic fingerprint could be used as a test to identify those who would respond well to conventional treatments and those with disease that has already started to spread. The test outperforms traditional methods of distinguishing these groups.
The second study, performed in collaboration with Dr. Boutros and Dr. Gail Risbridger (Monash University), focused on a group of men with an inherited form of the disease known as BRCA2-associated prostate cancer. The research team analyzed the genetic profiles of these tumours and found that certain pathways involved in cell growth were abnormally regulated. These abnormalities are similar to those typically found in non-inherited prostate cancer tumours that are resistant to therapy and that spread through the body. As such, the BRCA2-associated tumours are already aggressive even before treatment, suggesting that therapies to offset this aggressiveness should be considered earlier.
"This is an exciting time in prostate cancer research in which the genetics of individual men and their cancers are beginning to dictate precise and customized treatment," says Dr. Bristow. "These studies are examples of how international collaboration and team science can crack the genetic code of tumours."
You can watch Dr. Bristow discusses his research in this video.
These works were supported by the Movember Foundation, Prostate Cancer Canada, the Ontario Institute for Cancer Research (through the Government of Ontario), the Princess Margaret Hospital Radiation Medicine Program, the Canadian Cancer Society Research Institute Scientist Award, the Terry Fox Research Institute, the Canadian Institutes of Health Research, Genome Canada, the Natural Sciences and Engineering Research Council of Canada, the National Health and Medical Research Council of Australia, the Victorian State Government Cancer Agency, TissuPath, the Prostate Cancer Foundation of Australia, the National Breast Cancer Foundation, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, the Cancer Foundation of Western Australia and The Princess Margaret Cancer Foundation.
Fraser M, Sabelnykova VY, Yamaguchi TN, Heisler LE, Livingstone J, Huang V, Shiah YJ, Yousif F, Lin X, Masella AP, Fox NS, Xie M, Prokopec SD, Berlin A, Lalonde E, Ahmed M, Trudel D, Luo X, Beck TA, Meng A, Zhang J, D'Costa A, Denroche RE, Kong H, Espiritu SM, Chua ML, Wong A, Chong T, Sam M, Johns J, Timms L, Buchner NB, Orain M, Picard V, Hovington H, Murison A, Kron K, Harding NJ, P'ng C, Houlahan KE, Chu KC, Lo B, Nguyen F, Li CH, Sun RX, de Borja R, Cooper CI, Hopkins JF, Govind SK, Fung C, Waggott D, Green J, Haider S, Chan-Seng-Yue MA, Jung E, Wang Z, Bergeron A, Pra AD, Lacombe L, Collins CC, Sahinalp C, Lupien M, Fleshner NE, He HH, Fradet Y, Tetu B, van der Kwast T, McPherson JD, Bristow RG, Boutros PC. Genomic hallmarks of localized, non-indolent prostate cancer. Nature. 2017 Jan 9. doi: 10.1038/nature20788.
Taylor RA, Fraser M, Livingstone J, Espiritu SM, Thorne H, Huang V, Lo W, Shiah YJ, Yamaguchi TN, Sliwinski A, Horsburgh S, Meng A, Heisler LE, Yu N, Yousif F, Papargiris M, Lawrence MG, Timms L, Murphy DG, Frydenberg M, Hopkins JF, Bolton D, Clouston D, McPherson JD, van der Kwast T, Boutros PC, Risbridger GP, Bristow RG. Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories. Nature Communications. 2017 Jan 9. doi: 10.1038/ncomms13671.