Aggressive prostate cancer secrets revealed in landmark study

January 9, 2017, Monash University
Stylized image of prostate cancer from a man with a BRCA2 mutation. Credit: Monash University

A landmark study, led by Monash University's Biomedicine Discovery Institute with the involvement of the Peter MacCallum Cancer Centre, has revealed the reason why men with a family history of prostate cancer who also carry the BRCA2 gene fault have a more aggressive form of prostate cancer.

The study, published today in Nature Communications, involving a consortium of Melbourne and Toronto researchers and clinicians, reports the molecular profile of the prostate cancers in men with the BRCA2 fault is similar to the profile seen in patients with advanced cancer: explaining why - right from diagnosis - BRCA2 patients have a poor outcome.

The international team of scientists, led by Professor Gail Risbridger and Dr Renea Taylor from the Monash Biomedicine Discovery Institute (BDI) and Dr Rob Bristow from the Princess Margaret Cancer Centre in Toronto, Canada, in collaboration with clinicians from the Peter MacCallum Cancer Centre, kConFab, Austin Health and the Olivia Newton-John Cancer Centre, worked to unlock the secrets of why prostate cancer in BRCA2 men behaves aggressively.

This study, part of a larger Victorian Cancer Agency funded program of translational research, had previously reported that men who carried the BRCA2 gene fault were at a higher risk of having a more aggressive form of prostate cancer if a cell pathology known as IDCP (intraductal carcinoma of the prostate) was present; the IDCP cell pathology predicted these men were much more likely to have a poor clinical outcome.

The reason why this happens is now clear. Following surgery to remove the cancerous prostate, the patient's specimen was made available to the laboratory for genomic analyses. Surprisingly, the study showed that these early, untreated, were genetically similar to cancers that are usually seen in men with more advanced cancer that has spread to other parts of the body. This was in contrast to the cancers seen in men who don't carry a BRCA2 gene fault and who rarely have cancer spread at diagnosis. This was confirmed when compared to data from a companion study, published at the same time in Nature and led by the Toronto group, which looked at prostate cancer tissue samples from more than 320 patients with prostate cancer who don't carry a BRCA2 gene fault.

Professor Gail Risbridger and Dr Renea Taylor, Monash Biomedicine Discovery Institute. Credit: Steven Morton

Put together, these studies identified why the presence of the BRCA2 gene fault led to markedly different clinical outcomes, with the disease progressing rapidly in this group of men.

Director of Monash Partners Comprehensive Cancer Consortium and Monash BDI lead author, Professor Gail Risbridger, explained why these findings are important.

"This study shows how different these tumours are from 'regular' tumours and emphasises the importance of men knowing if they have a family history of prostate, breast or ovarian cancer in their family and may carry the BRCA2 gene fault," Professor Risbridger said.

Fellow Monash BDI lead author, Dr Renea Taylor, highlighted that these findings prompt the need to think about whether these men should be managed differently.

"As the tumours in men with the BRCA2 gene fault are so different from the 'get-go', our findings raise the question about whether these patients should be managed differently at diagnosis," Dr Taylor said.

Director of Genitourinary Oncology at the Peter MacCallum Cancer Centre and study author, Associate Professor Declan Murphy, spoke about possible therapeutic implications."We now know that the BRCA2 fault is seen in many more men presenting with advanced prostate cancer than previously realised. Also, as prostate cancer progresses, the BRCA2 fault begins to develop in prostate cancer secondaries, and drives the aggressive behaviour of the cancer. Therefore these new findings detailing the genomic instability of BRCA2 prostate cancer are important as we may be able to target this with new therapies," Associate Professor Murphy said.

Explore further: Prostate cancer researchers find genetic fingerprint identifying how, when disease spreads

More information: Renea A. Taylor et al, Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories, Nature Communications (2017). DOI: 10.1038/ncomms13671

Related Stories

Prostate cancer researchers find genetic fingerprint identifying how, when disease spreads

January 9, 2017
Canadian prostate cancer researchers have discovered the genetic fingerprint that explains why up to 30 per cent of men with potentially curable localized prostate cancer develop aggressive disease that spreads following ...

AUA: BRCA mutations may play role in prostate cancer

May 10, 2016
(HealthDay)—A man's risk of aggressive and fatal prostate cancer may be heavily influenced by gene mutations previously linked to breast and ovarian cancer in women, a trio of new studies suggests. Findings from the studies ...

Research helps explain why androgen-deprivation therapy doesn't work for many prostate cancers

January 5, 2017
Metastatic prostate cancer, or prostate cancer that has spread to other organs, is incurable. In new research published in the journal Science, Roswell Park Cancer Institute scientists have identified two gatekeeper genes ...

Inherited mutations in three genes predict for aggressive prostate cancer

December 15, 2016
A study of three genes associated with the development of prostate cancer found that men with inherited mutations in these genes are more likely to develop aggressive forms of the disease and die from prostate cancer at an ...

New findings concerning hereditary prostate cancer

July 11, 2016
It is a well-known fact that men with a family history of prostate cancer run an increased risk of developing the disease. The risk for brothers of men with prostate cancer is doubled. But a doubled risk of what, exactly? ...

Testing for inherited mutations could benefit men with advanced prostate cancer

July 6, 2016
Inherited mutations in genes that function to repair DNA may contribute to metastatic prostate cancer more than previously recognized, according to a study out today in the New England Journal of Medicine. Though infrequent ...

Recommended for you

Researchers create a drug to extend the lives of men with prostate cancer

March 16, 2018
Fifteen years ago, Michael Jung was already an eminent scientist when his wife asked him a question that would change his career, and extend the lives of many men with a particularly lethal form of prostate cancer.

Machine-learning algorithm used to identify specific types of brain tumors

March 15, 2018
An international team of researchers has used methylation fingerprinting data as input to a machine-learning algorithm to identify different types of brain tumors. In their paper published in the journal Nature, the team ...

Higher doses of radiation don't improve survival in prostate cancer

March 15, 2018
A new study shows that higher doses of radiation do not improve survival for many patients with prostate cancer, compared with the standard radiation treatment. The analysis, which included 104 radiation therapy oncology ...

Joint supplement speeds melanoma cell growth

March 15, 2018
Chondroitin sulfate, a dietary supplement taken to strengthen joints, can speed the growth of a type of melanoma, according to experiments conducted in cell culture and mouse models.

Improved capture of cancer cells in blood could help track disease

March 15, 2018
Tumor cells circulating throughout the body in blood vessels have long been feared as harbingers of metastasizing cancer - even though most free-floating cancer cells will not go on to establish a new tumor.

Area surrounding a tumor impacts how breast cancer cells grow

March 14, 2018
Cancer is typically thought of as a tumor that needs to be removed or an area that needs to be treated with radiation or chemotherapy. As a physicist and cancer researcher, Joe Gray, Ph.D., thinks differently.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.