Gene links rare and unrelated cancers

Vancouver, BC – A team of scientists at the BC Cancer Agency, Vancouver Coastal Health Research Institute, and the University of British Columbia have found mutations in rare, seemingly unrelated cancers were all linked to the same gene, known as DICER.

The team is led by Dr David Huntsman, genetic pathologist and director of the Ovarian Cancer Program of BC at the BC Cancer Agency and Vancouver Coastal Health Research Institute and Dr Gregg Morin, a lead scientist from the Michael Smith Genome Sciences Centre at the BC Cancer Agency.

The research team set about sequencing rare ovarian, uterine, and testicular tumours, expecting to find that their genomes would be distinct with specific, differing abnormalities. They discovered that the same fundamental mutation in the DICER gene showed up as the common process underlying all of the different cancers they examined.

The findings were published December 21 in the New England Journal of Medicine.

“DICER is of great interest to cancer researchers” says Dr Huntsman, who also holds the Dr Chew Wei Memorial Professorship in the departments of Obstetrics and Gynaecology and Pathology and Laboratory Medicine at UBC. “There have been nearly 1,300 published studies about it in the last 10 years, but until now, it has not been known how the gene functions in relation to cancer.”

The gene plays an important role in maintaining health. It chops up microRNA molecules to activate them. These microRNA molecules in turn control hundreds of other genes. “This discovery shows researchers that these mutations change the function of DICER so that it participates directly in the initiation of cancer, but not in a typical on/off fashion,” says Dr Morin, who is also assistant professor in the department of Medical Genetics at UBC. “DICER can be viewed as the conductor for an orchestra of functions critical for the development and behaviour of normal cells. The mutations we discovered do not totally destroy the function of DICER, rather they warp it-the orchestra is still there but the conductor is drunk.”

This finding is the third of a series of papers published recently in the New England Journal of Medicine in which the Ovarian Cancer Research team has used new genomic technologies to unlock the molecular basis of poorly understood types of ovarian cancer.

“Studying rare tumours not only is important for the patients and families who suffer from them but also provides unique opportunities to make discoveries critical to more common cancers-both in terms of personalized medicine, but also in applying what we learn from how we manage rare diseases to more common and prevalent cancers,” says Dr Huntsman “The discovery of the DICER mutation in this varied group of rare tumours is the equivalent of finding not the needle in the haystack, but rather the same needle in many haystacks.”

The research team is now working to determine the frequency and role of DICER mutations in other types of cancers and are expanding their collaboration to discover whether mutant DICER and pathways it controls can be modulated to treat both the rare cancers in which the mutations were discovered and more common cancers.