New genetic mutations found for non-Hodgkin lymphoma

BC Cancer Agency scientists have identified a number of new genetic mutations involved in non-Hodgkin lymphoma (NHL).

This massive cancer-sequencing study (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10351.html),published online in Nature will open a floodgate for researchers around the world to explore the significant number of newly discovered gene mutations and their role in the growth and development of lymphoma cells.

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In an extensive undertaking, researchers sequenced the entire genome of lymphoma cancer cells from 14 NHL patient samples and the 'active' genes from 117 NHL patients to search for genetic mutations specific to cancer cells. The magnitude of data revealed 109 genes with recurring mutations, from which 26 have been identified as contributors to NHL based on their mutation patterns. More than two-thirds of mutated genes had never been linked to lymphoma prior to this study.

"Based on the patterns of mutation in these 26 genes, we can see that these mutations enable tumour cells to grow and expand in non-Hodgkin lymphoma patients," said Ryan Morin, the study's lead author and researcher at the BC Cancer Agency. "The mutated genes we've discovered, most of which were previously unknown to lymphoma or other cancers, should enable us to design new tests that allow us to recognize subtypes of lymphoma and may help us predict how each variation of this disease will react to different treatments."

Non-Hodgkin lymphoma is the fifth most common form of cancer in Canada, affecting 7,700 people in 2011 across the country. It estimated that more than 1,000 people in B.C. will be diagnosed this year.

"This research offers an exciting future for lymphoma survivors, who rely on research that could lead to new treatments," added Richard Alexander, chair, BC Chapter of the Leukemia Lymphoma Society, and who has lived with lymphoma for nearly 30 years and received treatment at the BC Cancer Agency. "It is especially gratifying that this research was accomplished by many local scientists."

The pattern of mutation observed in some of these genes is indicative of new tumour suppressors and oncogenes, the latter of which may be ideal targets for existing therapies. Specifically, one of the novel lymphoma-related genes discovered in this study, MLL2, is mutated in 89 per cent of Follicular lymphoma patients, suggesting it is the most commonly mutated gene in NHL. Mutation of MLL2, which appears to be a tumour suppressor, is suspected to provide cancer cells with the ability to grow rapidly in-spite of the body's regulatory mechanisms. A second novel gene discovery, MEF2B, bears a so-called 'hot spot' mutation pattern reminiscent of other known cancer genes.

This major advancement in lymphoma knowledge comes on the heels of three other significant discoveries within the past 18 months from the BC Cancer Agency's lymphoid research group, who is drawing international attention from fellow researchers.

Their team recently launched a major new research initiative, the ANGELYC Project, which will analyze the entire DNA of all lymphoid cancers, to discover and develop new, targeted, and more effective treatments for patients. The BC Cancer Foundation has raised $2.6 million to support this momentous project.

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