Vancouver, BC – Scientists from the BC Cancer Agency have discovered a never before seen DNA spelling mistake, or mutation, in a gene called EZH2 in diffuse large B-cell lymphoma and follicular lymphoma, the two most common types of non-Hodgkins lymphoma.
This groundbreaking discovery, which was published online on January 17 in the prestigious international science journal Nature Genetics, is of particular importance because cancer related mutations (DNA spelling mistakes) are often observed in different sites in genes associated with individual tumours while this mutation is found in exactly the same location in samples from different lymphoma patients. Based on previous research, the mutated site is known to be one of the most important amino acids in the proper functioning of EZH2.
“Lymphoma is the fifth most common form of cancer and has the fastest growth rate of any common cancer in North America,” said Health Services Minister Kevin Falcon. “The breakthrough by the scientists involved in this study is an important step to better understanding the disease and gives hope that new treatments can be found.”
“While we know EZH2 is involved in certain types of breast and prostate cancer, it has never before been found mutated in any cancer and was not previously implicated in having a role in lymphomas,” said Dr. Joseph Connors, Chair of the Lymphoma Tumour Group and Clinical Director of the Centre for Lymphoid Cancer at the BC Cancer Agency, an agency of the Provincial Health Services Authority, and Clinical Professor, Medical Oncology, University of British Columbia. “The presence of this mutation can be considered a marker that will aid in diagnosing these lymphomas and identifying new therapies for their treatment.”
In addition to decoding thousands of genes in malignant cells from 31 patients with diffuse large B-cell lymphoma, the entire genome of a patient with follicular lymphoma was decoded. When researchers found the EZH2 mutation in exactly the same position in many of the cases, they examined the malignant cells of additional patients and found it to be mutated the same way and in the same position in almost one quarter of the cases with a specific lymphoma subtype.
“Usually spelling mistakes are observed in different sites in individual tumours rather than affecting exactly the same part of the gene as we have found with EZH2 in this study,” added Dr. Randy Gascoyne, Hematopathologist and Research Director, Centre for Lymphoid Cancers at the BC Cancer Agency, and Clinical Professor, Pathology and Laboratory Medicine, University of British Columbia. “This will allow for the development of medications that target only the cancerous cells and will be harmless to healthy cells.”
The discovery was made in collaboration with the BC Cancer Agency’s Genome Sciences Centre, whose next-generation DNA sequencing machines are able to decode billions of nucleotides at rapid speed and whose new computer techniques allow rapid interpretation of data.
“The technological advancements in DNA sequencing have allowed us to do in a matter of weeks what used to take years and at a fraction of the cost. The clear benefit to patients is the opportunity to design new approaches to treatment,” said Dr. Marco Marra, Director, BC Cancer Agency’s Genome Sciences Centre and Professor, Department of Medical Genetics, University of British Columbia.
This year an estimated one thousand British Columbians will be diagnosed with non-Hodgkin’s lymphoma and 340 will die of it. Diffuse large B-cell lymphoma is an aggressive cancer that can only be cured in about two thirds of patients while follicular lymphoma is a slower growing cancer for which there is currently no cure but which can be kept in check for long periods of time with relatively mild chemotherapy.
“The generation of knowledge through research is an integral part of our mission,” said Dr. David Levy, President, BC Cancer Agency. “By investing in research to indentify the causes of cancers like lymphoma, we are able to find better treatments to give patients longer life, and a better quality of life.”
“I have been living with follicular lymphoma for more than seven years and have already seen firsthand the difference improvements in treatment can make,” said Paul McDonald, a patient in remission for more than five years. “I know I will probably have to deal with it again in the future and this discovery gives me hope that there will be a cure for this long-term chronic disease.”
The study was funded in part by grants from the National Cancer Institute Office of Cancer Genomics (USA), the National Cancer Institute of Canada, the Terry Fox Foundation’s New Frontiers program, Genome Canada/Genome BC funding, the Michael Smith Foundation for Health Research, the Leukemia & Lymphoma Society and the Canadian Institutes for Health Research. Research conducted at the BC Cancer Agency is generously supported by donors to the BC Cancer Foundation.
The BC Cancer Agency, an agency 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 Foundation raises funds to support research and enhancements to patient care at the BC Cancer Agency. www.bccancer.bc.ca
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