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Subtle changes in PTEN tumor suppressor gene can determine cancer susceptibility
Date:4/23/2010

BOSTON It is an accepted fact that genetics play a key role in a person's susceptibility to cancer, and that throughout life, mutations can cause damage to tumor suppressor genes (TSGs) further increasing the chances of developing cancerous tumors.

Now a new study led by scientists at Beth Israel Deaconess Medical Center (BIDMC) demonstrates that even subtle changes in expression of the PTEN tumor suppressor gene can significantly increase cancer susceptibility in specific tissues, suggesting that environmental factors, such as diet or exposure to carcinogens, may have a more dramatic influence on tumor development than previously recognized. Appearing in this week's Advance On-line issue of Nature Genetics, the findings propose a new model for the role of tumor suppressor genes in the onset of cancer and could prove valuable in the development of diagnostic tests targeted to these gene alterations.

"More than 30 years ago, it was proposed that a person's susceptibility to cancer was dependent on a 'two-hit' model," explains Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Genetics Program at BIDMC and George C. Reisman Professor of Medicine at Harvard Medical School. This meant that there had to be two genetic alterations of a single tumor suppressor gene (TSG) to activate tumor development one gene would be missing from birth, while the second would be lost to other factors during one's lifetime.

"Our study adds another dimension to this Knudsonian model [so-named for its creator, cancer geneticist Alfred Knudson] demonstrating that cancer susceptibility can be driven in specific tissues by a progressive -- but slight -- continuum reduction in tumor suppressor levels," explains Pandolfi. "Consequently, subtle modulation of TSG levels can result in increased cancer susceptibility. This implies that any factor that affects PTEN levels chemicals, diet, other carcinogens could increase tumor susceptibility, even in t
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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