Science and Law
17th March 2016

BAP1 Genomic Mouse Studies Provide Important Clues to the Cause of Malignant Mesothelioma

BRCA1-associated protein (commonly referred to as BAP1) is a tumor suppressor or a “cellular stop sign” that tells cells to stop dividing when something in the cell goes wrong, such as when cancer arises. A mutated BAP1 gene makes a mutant version of the protein, which performs abnormal functions in the body.

BAP1 Genomic Mouse Studies Provide Important Clues   to the Cause of Malignant Mesothelioma

About five years ago, scientists began trying to explain why different individuals seem to have variable susceptibilities to mesothelioma (i.e., why do some individuals develop cancer when exposed to very low levels of asbestos, while others who have been exposed to very high levels of asbestos do not develop cancer?).

BRCA1-associated protein (commonly referred to as BAP1) is a tumor suppressor or a “cellular stop sign” that tells cells to stop dividing when something in the cell goes wrong, such as when cancer arises. A mutated BAP1 gene makes a mutant version of the protein, which performs abnormal functions in the body. One abnormal function could be to increase an organism’s susceptibility to cancer or to increase its susceptibility to the carcinogenic effects of asbestos.

Mesothelioma in Human Populations with BAP1 Mutations

An important discovery relevant to asbestos litigation emerged when Testa and Carbone (2011) discovered that germline BAP1 mutations (i.e., inherited mutations) were found in two American families with MM. Moreover, Testa and Carbone found that those two families had extremely high rates of MM, as well as other cancers, without ever having been exposed to asbestos.

These findings by Testa and Carbone were consistent with the view that a genetic susceptibility factor—BAP1 mutations—might account for certain individuals’ increased likelihood of developing MM even without asbestos exposure. This meant not only that the malignant tumors they studied had a genetic defect but also that the individuals with those tumors had an inherited defect that increased their risk of developing MM.

Since 2011, research on the BAP1 tumor suppressor gene in the context of asbestos exposure and MM susceptibility has expanded greatly. One theory posits that MM may occur more frequently in asbestos-exposed individuals who have a germline BAP1 mutation. What is striking, however, is that most families examined during recent studies have not had occupational exposure to asbestos. In fact, the majority of families in such studies have had no known exposure to asbestos at all. These observations have led researchers to believe that BAP1 mutations alone may predispose individuals to MM in cases where exposure to asbestos is no higher than background levels.

 

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