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MIT biologists pinpoint a genetic change that helps tumors move to other parts of the body
Date:4/6/2011

CAMBRIDGE, Mass. -- MIT cancer biologists have identified a genetic change that makes lung tumors more likely to spread to other parts of the body. The findings, to be published in the April 6 online issue of Nature, offers new insight into how lung cancers metastasize and could help identify drug targets to combat metastatic tumors, which account for 90 percent of cancer deaths.

The researchers, led by Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research at MIT, found the alteration while studying a mouse model of lung cancer. They then compared their mouse data to genetic profiles of human lung tumors and found that reduced activity of the same gene, NKX2-1, is associated with higher death rates for lung-cancer patients.

This study represents an important step in understanding how changes that disable this gene would make tumors more aggressive, says Monte Winslow, a senior postdoctoral associate in Jacks' lab and lead author of a paper.

Understanding the role of NKX2-1 may help scientists pursue drugs that could counteract its loss. Right now, "the sad reality is that if you could tell a patient whether their cancer has turned down this gene, you would know they will have a worse outcome, but it wouldn't change the treatment," Winslow says.

Winslow and his colleagues at the Koch Institute studied mice that are genetically programmed to develop lung tumors. The mice's lung cells can be induced to express an activated form of the cancer-causing gene Kras, and the tumor suppressor gene p53 is deleted. While all of those mice develop lung tumors, only a subset of those tumors metastasizes, suggesting that additional changes are required for the cancer to spread.

The researchers analyzed the genomes of metastatic and non-metastatic tumors in hopes of finding some genetic differences that would account for the discrepancy. The absence of NKX2-1 activity in metastatic tumors was
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Contact: Patti Richards
prichards@mit.edu
Massachusetts Institute of Technology
Source:Eurekalert

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