When the group began sequencing the genomes of these and other rare tumours, they expected to find different gene mutations in each form of the disease. However, they were amazed to discover that the same fundamental mutation in the DICER gene showed up in multiple tumour types.
The findings are published today in the New England Journal of Medicine. Dr. Huntsman was interviewed by CTV about this study; you can view the video clip here or read more about it in the National Post or Vancouver Sun.
“DICER is of great interest to cancer researchers”, says Dr. Huntsman. “There have been nearly 1300 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 has as a “factory style” function, chopping 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 study co-leader Dr. Gregg Morin of the BC Cancer Agency’s Michael Smith Genome Sciences Centre. “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.”
“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 of the 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.
The Michael Smith Genome Sciences Centre, located at the BC Cancer agency, played a key role in this discovery. A decision was made more than 10 years ago, championed by Drs. Michael Smith, Victor Ling, and others to create and locate this facility within the BC Cancer Agency and in close proximity to Vancouver General Hospital. This location has enabled the multidisciplinary cancer research teams in Vancouver access to state of the art technologies and that is now paying off.
“We are one of less than five places in the world doing this type of work successfully. This discovery is one of a series of recent landmark findings from Vancouver that are reshaping our understanding of many cancers,” says Dr. Huntsman. “Since my arrival in Vancouver 20 years ago I have never before sensed such a strong feeling of communal pride and excitement within our research community. Our next task is to bring the discoveries into the clinic.”
This study was supported through funding by Canadian Institutes for Health Research, Terry Fox Foundation, BC Cancer Foundation, VGH & UBC Hospital Foundation, Michael Smith Foundation for Health Research, and Genome BC.
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