A consortium of Cancer Research UK scientists and doctors, along with researchers at the BC Cancer Agency and Vancouver Coastal Health Research Institute, has discovered a new gene for breast and ovarian cancer – providing a missing link in an enduring medical mystery.

The gene, which they have named EMSY, finally joins the dots between hereditary breast cancers and sporadic, non-inherited forms.

While inheriting faulty BRCA genes can trigger hereditary breast and ovarian cancer, no one could find a role for these genes within sporadic tumours.

But the new study – in the leading journal Cell tomorrow (Wednesday) – finally provides a solution, suggesting EMSY shuts down the action of functional BRCA2 to fuel cancer's development. It is not only a key advance in understanding how and why cancers develop, but may pave the way for new types of test to predict how the disease may progress.

Identifying the new gene and linking it to many cases of breast and ovarian cancer is the culmination of six years work for two teams of Cancer Research UK researchers.

Cancer Research UK's Professor Tony Kouzarides, who led the project at the Wellcome Trust/Cancer Research UK Institute, University of Cambridge, says: "Discovering such an important new gene is very exciting and gives us the piece in the jigsaw we've been looking for.

"We'll now have a much more sophisticated image of the genetic changes triggering breast and ovarian cancer in women who haven't inherited a high risk of cancer, but develop it anyway. It's going to give us new lines of investigation and potentially exciting angles of attack."

Inheriting faulty BRCA genes gives women a high risk of breast and ovarian cancer, but only five per cent of breast cancers run in families like this. Scientists have been hunting for the genes that cause sporadic breast cancers – the other 95 per cent of cases – ever since the BRCA genes were discovered, eight years ago.

They had long suspected BRCA2 might play a role in sporadic breast and ovarian cancers, despite the fact that the gene is very rarely damaged within these tumours.

Professor Kouzarides' team searched for sequences of DNA that interact with BRCA2 and were able to describe and isolate a brand new gene. They decided to call the gene EMSY after cancer nurse Emma Hughes-Davies - the sister of Dr Luke Hughes-Davies, the discoverer of the gene and a Cancer Research UK clinical fellow.

Scientists found that EMSY has a role in turning genes on and off and in repairing damaged DNA. It is highly effective at switching off BRCA2, raising suspicions that it might be an important cancer gene.

Colleagues at the Cancer Research UK Department of Oncology, University of Cambridge, were convinced they were on the right track to a new cancer gene when they found extra copies of EMSY in the first few tumour samples they tested.

Working with a team from the BC Cancer Agency (BCCA) and Vancouver Coastal Health Research Institute (Vancouver General Hospital site), they then analysed the gene in nearly 551 breast and 360 ovarian tumours. Their suspicions were confirmed - they found extra copies of the gene in 13 per cent of breast cancers and 17 per cent of ovarian cancers, but never in normal tissue and hardly ever in other types of tumour. This work was done at the Genetic Pathology Evaluation Centre (GPEC), a BCCA and VCHRI collaborative lab, which was specifically created to perform this kind of analysis.

"Abnormalities in this gene are strongly associated with aggressive behaviour in breast and ovarian cancers," says Dr. David Huntsman, one of the BC Cancer Agency researchers. "Therefore, the gene holds great promise as a prognostic test for cancer patients, and perhaps as a target for new drugs."

Adds Dr. Blake Gilks, researcher with the Vancouver Coastal Health Research Institute, "This research was possible due to the efforts of the BCCA breast tumour group and the OvCaRe ovarian cancer research group to create centralized patient databases. We were able to link patient data to an extensive archive of cancer tissue samples using a technique called tissue microarray analysis. We look forward to working with other leading-edge investigators, including those locally such as at the BCCA and the Prostate Centre at VGH to determine the clinical relevance of their research discoveries. The GPEC, as a research resource, is unparalleled in scope and potential and competitive with the best in the world."

EMSY seems to play a particularly important role in aggressive forms of breast cancer. Women whose tumours had extra copies of the EMSY gene survived for

6.4 years on average, compared with 14 years for those whose breast cancers had normal amounts of EMSY.

The difference in survival was particularly great among women who at diagnosis had not suffered any spread of the cancer to their lymph nodes, suggesting it might be possible to test for EMSY early on in a woman's course of treatment, in order to predict how aggressive their disease is likely to become.

Professor Robert Souhami, Cancer Research UK's Director of Clinical and External Affairs, says: "This is really exciting stuff – discoveries like this don't come along very often and it's taken a major collaborative effort.

"It's very appropriate that EMSY is named after a woman, because it's a gene which is exclusively important in women's cancers and will hopefully bring significant advances in treating female cancer patients."

For Canadian and U.S. media enquiries, please contact Nicole Adams, Public Relations Officer, BC Cancer Agency, at 604.877.6272.

For international media enquiries, please contact Richard Hoey in Cancer Research UK's press office on 0207 061 8300/8308 or, out-of-hours, the duty press officer on 07050 264 059.

Women who inherit a damaged BRCA2 gene have a 40-60 per cent chance of developing breast cancer at some time in their lives and a 10-20 per cent chance of getting ovarian cancer.

EMSY's protein contains the sequence of amino acids serine-isoleucine-serine-threonine-glutamic acid-arginine, which in standard abbreviations spells out S-I-S-T-E-R. It was this that inspired the researchers to name the gene after one of their sisters.

Having extra copies of EMSY seems to have much the same effect as not having enough functional BRCA2 – leaving breast and ovarian cells highly vulnerable to turning cancerous. Scientists believe BRCA2 may be important for repairing damage to DNA and when inactivated, may leave cells open to the cancer-causing effects of genetic damage.

The BC Cancer Agency, a part of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. The BC Cancer Research Centre conducts research into the causes and cures for cancer

The Vancouver Coastal Health Research Institute (VCHRI) is as a joint venture between the University of British Columbia and Vancouver Coastal Heath. The Institute serves as the public face of research and promotes the development of all research activity. Major programs include the Prostate Research Centre; the Brain Research Centre; ICORD; and the Ike Barber Lab for Diabetes. VCHRI investigators are at the forefront of research activity. Through their leading-edge work, better health outcomes and healthier lives can and will be achieved.