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2002/07/08: Discovery in worms may provide clue to breast cancer development

VANCOUVER, B.C. - Scientists at the BC Cancer Agency have discovered a novel mechanism of how breast cancer might develop. These findings are reported today in the prestigious journal Nature Genetics.

The finding is related to "G-quartets," an unusual grouping of one of the bases that form DNA – the blueprint of human life. Normally, the base G (for guanine), is linked with the base C (for cytosine). In G-quartets, Gs link together in a very stable knot. The research found that an enzyme is required to prevent the loss of G-rich DNA when it forms a G-quartet. When DNA is lost, important genetic information or material may be left out, and the proper function of a cell may be compromised.

"The specialized enzyme is an example of a molecule that's essential to maintain DNA," explains Iris Cheung, a second year graduate student at the Terry Fox Laboratory of the BC Cancer Agency. "If it is lost, then there are problems at multiple sites in the genome."

Dr. Peter Lansdorp's team at the BC Cancer Agency's Terry Fox Lab has been working in collaboration with Dr. Ann Rose of UBC on an C. elegans worm model to study the G-quartet in living beings.

Such G-quartets have been observed with purified DNA in the laboratory for some time, but this is the first evidence that this structure actually exists in the cells of a living organism – in this case the C.elegans worm.

The BC Cancer Agency researchers discovered recurrent abnormalities associated with G-quartet formation in the C. elegans worm, which lacks the specialized enzyme – called a helicase. The team found these abnormalities throughout the DNA of helicase deficient worms.

Most tumour cells have multiple genetic abnormalities. It has been shown that DNA repair genes are often involved. This is because abnormalities in such genes result in cells that are genetically unstable. Presumably, this instability is what turns normal cells into tumour cells.

The helicase in the worm has a good match in humans: a protein that interacts with BCRA1, and shows abnormalities in a number of patients with breast cancer. Studies of this gene in humans and mice is proceeding rapidly in Dr. Lansdorp's lab.

"These molecules are needed to maintain the genetic integrity in cells, and without this integrity, cancer has a chance to develop," explains Dr. Lansdorp, senior scientist at the Terry Fox Laboratory.

Nature Genetics is one of the most prestigious journals for biomedical research, and has the highest impact factor of all life sciences journals. The BC Cancer Agency, a part 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 Research Centre conducts research into the causes and cures for cancer.

For more information, or to arrange an interview, please contact:
Nicole Adams
Public Relations Officer
BC Cancer Agency
(604) 877-6272