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Study offers new theory of cancer development
Date:10/31/2013

cesses such as cell division and DNA repair.

To test their hypothesis, the researchers developed a computer program called TUSON (Tumor Suppressor and Oncogene) Explorer together with Wei Xu and Peter Park at HMS and Brigham and Women's. The program analyzed genome sequence data from more than 8,200 pairs of cancerous and normal tissue samples in three preexisting databases.

They generated a list of suspected oncogenes and tumor suppressor genes based on their mutation patternsand found many more potential cancer drivers than anticipated. Then they ranked the suspects by how powerful an effect their deletion or duplication was likely to have on cancer development.

Next, the team looked at where the suspects normally appear in chromosomes.

They discovered that the number of tumor suppressor genes or oncogenes in a chromosome correlated with how often the whole chromosome or part of the chromosome was deleted or duplicated in cancers. Where there were concentrations of tumor suppressor genes alongside fewer oncogenes and fewer genes essential to survival, there was more chromosome deletion. Conversely, concentrations of oncogenes and fewer tumor suppressors coincided with more chromosome duplication.

When the team factored in gene potency, the correlations got even stronger. A cluster of highly potent tumor suppressors was more likely to mean chromosome deletion than a cluster of weak suppressors.

Number matters

Since 1971, the standard tumor suppressor model has held that cancer is caused by a "two-hit" cascade in which first one copy and then the second copy of a gene becomes mutated. Elledge argues that simply losing or gaining one copy of a gene through aneuploidy can influence tumor growth as well.

"The loss or gain of multiple cancer driver genes that individually have low potency can add up to have big effects," he said.

"It's a terrific study," said Angelika Amon, a profe
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Contact: David Cameron
david_cameron@hms.harvard.edu
617-432-0441
Harvard Medical School
Source:Eurekalert

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