Healthy-looking prostate cells mask cancer-causing mutations

New findings published today in Nature Genetics show that in some men who have prostate cancer, non-cancerous prostate cells that appear normal under the microscope can have lots of different genetic mutations.

The research – funded by Cancer Research UK, the Dallaglio Foundation and the Wellcome Trust – prompts new ways to improve treatment for the disease.

Prof Colin Cooper, from UEA’s Norwich Medical School, said: “Prostate cancer is often made up of many small tumours with different genetic fingerprints, and it is still unclear what causes these different tumours to develop in the prostate at the same time. But this new research provides a piece of the puzzle that could help solve the mystery.

“The results suggest that large numbers of normal-looking prostate cells have a variety of genetic faults and cancer could develop from any of them. This could explain why prostate cancer is often made up from multiple genetically different tumours and suggests that prostate cancer development begins earlier than scientists thought.”

The findings may lead to a rethink of prostate cancer treatment, in which these pre-cancerous cells are destroyed at the same time as the tumour cells.

Co-author Daniel Brewer, from Norwich Medical School and The Genome Analysis Centre (TGAC) at Norwich Research Park, said: “This study has sequenced the whole genetic sequences of multiple samples from the prostate for the first time – both from tumours and apparently normal tissue.

“Surprisingly there were a large number of abnormal genetic changes found in the normal prostate tissue, suggesting that the prostate as a whole is a hot bed of genetic instability and is primed and ready for tumours to develop. This gives us important clues to how prostate cancer develops and has potential consequences to how it is treated.”

The research forms part of the International Cancer Genome Consortium (ICGC), a global project using the latest genome sequencing technology to reveal the genetic changes driving the disease. Cancer Research UK scientists are mapping the genetic history of prostate and oesophageal cancers as part of this international effort.

Prof Peter Johnson, Cancer Research UK’s chief clinician, said: “As we learn more about cancer, we discover just how complex an enemy it is. But we’re developing the tools that can help reveal precancerous cells. And the next step will be to establish treatments that prevent them developing into cancer.

“This latest research provides powerful new insights into prostate cancer that we hope will one day help more men beat the disease.”

‘Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue’ is published in Nature Genetics on March 2, 2015.

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