MSH2-deficient prostate tumours have a distinct immune response and clinical outcome compared to MSH2-deficient colorectal or endometrial cancer
Patrick McCoy, Stefano Mangiola, Geoff Macintyre, Ryan Hutchinson, Ben Tran, Bernard Pope, Peter Georgeson, Matthew KH Hong, Natalie Kurganovs, Sebastian Lunke, Michael J Clarkson, Marek Cmero, Michael Kerger, Ryan Stuchbery, Ken Chow, Izhak Haviv, Andrew Ryan, Anthony J Costello, Niall M Corcoran, Christopher M Hovens
PROSTATE CANCER AND PROSTATIC DISEASES | SPRINGERNATURE | Published : 2021
BACKGROUND: Recent publications have shown patients with defects in the DNA mismatch repair (MMR) pathway driven by either MSH2 or MSH6 loss experience a significant increase in the incidence of prostate cancer. Moreover, this increased incidence of prostate cancer is accompanied by rapid disease progression and poor clinical outcomes. METHODS AND RESULTS: We show that androgen-receptor activation, a key driver of prostate carcinogenesis, can disrupt the MSH2 gene in prostate cancer. We screened tumours from two cohorts (recurrent/non-recurrent) of prostate cancer patients to confirm the loss of MSH2 protein expression and identified decreased MSH2 expression in recurrent cases. Stratifying ..View full abstract
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Awarded by NHMRC
KC is supported by a Postgraduate Medical Research Scholarship from the Prostate Cancer Research Fund, Foundations for Surgery Research Scholarship from the Royal Australasian College of Surgeons, and the Research Training Program Scholarship from the Australian Commonwealth Government. NMC is supported by a Movember - Distinguished Gentleman's Ride Clinician Scientist Award through Prostate Cancer Foundation of Australia's Research Program. MK was supported by the Carlo Vaccari Scholarship and APCR. SM was supported by the David Mayor PhD. Scholarship from the Prostate Cancer Research Foundation, and by the Pamela Galli Single Cell & Computational Genomics Initiative. NK was supported by a PhD scholarship from Australian Prostate Cancer Research. PM was supported by a PhD scholarship from Australian Department of Health and Ageing to the Epworth Cancer Centre, Epworth Hospital. PG is supported by an Australian Government Research Training Program Scholarship. BP is supported by a Victorian Health and Medical Research Fellowship. This work was supported by NHMRC project grants 1104010 (CMH, AJC, NMC) and 1047581 (CMH, AJC, NMC), as well as a federal grant from the Australian Department of Health and Ageing to the Epworth Cancer Centre, Epworth Hospital (AJC, NMC, CMH). In carrying out this research, we received funding and support from Australian Prostate Cancer Research and the University of Melbourne, Australia.