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Multicenter study nets new lung tumor-suppressor gene

BOSTON--Collaborating scientists in Boston and North Carolina have found that a particular gene can block key steps of the lung cancer process in mice. The researchers report in the journal Nature that LKB1 is not only a "tumor-suppressor" gene for non-small cell lung cancer in mice, it also may be more powerful than other, better-known suppressors. The study will be published on the journal's Web site on Aug. 5 and later in a print version.

If further research shows LKB1 has a similar effect in human lung cells, it could influence the way non-small cell lung cancer is diagnosed and treated, says the study's senior author, Kwok-Kin Wong, MD, PhD, of Dana-Farber, one of three institutions, along with Massachusetts General Hospital and the University of North Carolina School of Medicine, leading the work. If tumors with LKB1 mutations are found to be especially fast-growing, for example, patients with such tumors might be candidates for more aggressive therapy.

People born with defective versions of LKB1 often develop Peutz-Jeghers syndrome, which is marked by intestinal growths and an increased risk for certain cancers. Non-inherited mutations of the gene have been found in some lung cancers. This suggested that LKB1 normally thwarts tumors from forming. Mutated versions may be unable to act as a brake on cancer.

To find out, the investigators ran a series of experiments in mice with a defective form of a gene called Kras, which drives the formation and growth of lung cancer. They tracked the development of lung cancer in animals with mutated LKB1 and compared it to the experience of animals with abnormalities in either of two well-known tumor-suppressor genes.

They found that while Kras "cooperated" with the mutated tumor-suppressor genes to produce lung cancer, it cooperated even more strongly with mutated LKB1. The LKB1-deficient tumors grew more rapidly and spread more frequently than the others, and comprised all three
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
5-Aug-2007


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