A new gene for breast and ovarian cancer has been identified, which explains the link between hereditary and “sporadic” (non-inherited) forms of these cancers.
It has been known for some time that mutations in the BRCA1 and BRCA2 genes are associated with inherited breast and ovarian cancer. However, only 5% of breast cancers are inherited and no role had been found for these genes in non-inherited cancers.
Researchers have been hunting for the genes associated with sporadic breast cancers—95% of cases—ever since the BRCA genes were first identified, eight years ago.
Research published this week has identified a new gene, EMSY, which binds to normally functioning BRCA2, potentially triggering the development of cancer (Cell 2003;115: 523-514651845).
EMSY was isolated by researchers from the Wellcome Trust/Cancer Research UK Institute, at the University of Cambridge, when they were looking for sequences of DNA that interacted with BRCA2. The new gene proved to have a role in switching genes on and off and in repairing damaged DNA—relocating to sites of DNA damage.
Figure 1.
The new gene EMSY is named after breast cancer nurse Emma Hughes-Davies (above), wh o was called Emsy when she was a child
Credit: CANCER RESEARCH UK
It was found to be particularly effective at switching off BRCA2, raising suspicions that it might be an important cancer gene. This suspicion was strengthened when colleagues at the Cancer Research UK's department of oncology at Cambridge University found extra copies of EMSY in the first few tumour samples that they tested.
Working with a team at the British Columbia Cancer Agency in Canada, the Cambridge group then analysed EMSY in more than 500 breast and 300 ovarian tumours. They found that the gene was amplified in 13% of breast cancers and 17% of ovarian cancers, but never in normal tissue and very rarely in other types of tumour.
One of the research group, Dr Luke Hughes-Davies, a Cancer Research UK clinical scientist at Addenbrooke's Hospital, Cambridge, said: “The remarkable clinical overlap between sporadic EMSY amplification and familial BRAC2 deletion—which only occurs in breast and ovarian tumours—implicates a BRCA2 pathway in sporadic breast and ovarian cancers.”
The discovery of EMSY has several important clinical implications. EMSY amplification was found to be associated with a poor prognosis, particularly in node-negative breast cancer. Women whose tumours showed increased expression of EMSY had an average survival of 6.4 years, compared with 14 years for women whose breast cancers showed normal levels of EMSY. This suggests that it might be of prognostic value. The gene also offers a new target for the development of new treatments for breast and ovarian cancer.
The sequence of the first few amino acids of the protein coded for by EMSY—serine, isoleucine, serine, threonine, glutamic acid, and arginine—spells out the word “sister” when the standard abbreviations for these amino acids are used. So, the researchers named the gene after the sister of one of the members of the research group, Dr Hughes-Davies (Emma Hughes-Davies, known as Emsy when she was young). This was particularly appropriate as Ms Hughes-Davies is a breast cancer nurse.