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Study shows that mutations in 1 gene cause many cancers
Date:3/29/2010

ell.

"Mutations in this gene also play a role in developmental disabilities and perhaps in autism, so this mouse model might be useful for studies in those conditions, as well," says co-principal investigator Michael Ostrowski, professor and chair of molecular and cellular biochemistry at Ohio State.

For this study, Leone, Ostrowski and their colleagues developed three strains of genetically identical mice, each of which had one of three specific PTEN mutations found in people with Cowden syndrome. This left each strain with a different version of the PTEN protein. The study showed that each version functioned in a different way, and each influenced cancer development to a different degree.

Mutation 1 disabled the protein altogether and often caused cancer in the animals, while mutation 2 produced a protein that was more active than the normal PTEN protein, and sometimes caused cancer. Mutation 3 altered the protein in ways that should have made it more cancer-causing but also made it more fragile, so less of the protein was present to cause problems. This mutation sometimes didn't cause cancer at all.

Using a database of more than 400 patients with Cowden syndrome, the researchers found that patients with these same mutations have cancer in the corresponding organs as the mice. The mice also showed equivalent gender differences in tumor development, with females developing more thyroid tumors, and males developing more adrenal gland and stomach tumors.

The researchers are now investigating why patients may experience differences in cancer severity even when they have the same mutation.


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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

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