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Gene identified for spread of deadly melanoma
Date:11/4/2010

of metastasis. In addition, 90 percent of class 2 tumors have lost a copy of chromosome 3, unlike class 1 tumors, which tend to retain both copies of the chromosome.

In this study, the team looked for differences in genes on chromosome 3 between the cells in class 1 and class 2 tumors. They started with tissue taken from a pair of class 2 tumors.

"We looked for common genetic differences, called polymorphisms, that would unlikely have much of an effect," Bowcock says. "We eliminated those variations and then went back to look at which gene on chromosome 3 had additional alterations. There was one gene, called BAP1, that had mutations in both of the tumors we analyzed."

BAP1 is short for BRCA1-associated protein 1. As it happens, BRCA1 is linked to breast cancer in some women.

"It points, possibly, to a common theme in cancer genetics," Bowcock says. "After identifying mutations in BAP1 in the first two tumors, we went back and looked at DNA from another 29 class 2 tumors, as well as 25 class 1 tumors. And we found that 84 percent of the class 2 tumors had damaging mutations in BAP1. We also found that in most cases, the class 2 tumor cells had only one copy of chromosome 3 where the gene is located so patients had only a single copy of the BAP1 gene, and because of damaging mutations, it could not fulfill its proper role in the cell."

It appears that what the gene is supposed to do, Harbour says, is to act as a metastasis suppressor. When it is damaged, the tumor can spread.

"There are several ways this discovery could improve patient care," Harbour says. "If we could detect BAP1 mutations at an earlier stage, for example, we might be able to monitor a patient's blood for detectable melanoma cells as an early sign that they're developing metastatic disease."

He also says a better understanding of the normal role of the BAP1 protein could provide powerful insights into ways to therapeutically target eye
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Contact: Jim Dryden
jdryden@wustl.edu
314-286-0110
Washington University School of Medicine
Source:Eurekalert  

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