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Timothy W Grosel, Getachew Boru, James Massengill, Frederick H Davidorf, Colleen M Cebulla, Mohamed H Abdel-Rahman; Mechanisms of somatic biallelic inactivation of BAP1 in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5895. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Biallelic somatic activation of BAP1 is common in uveal melanoma (UM) and is associated with more aggressive tumor. The mechanism of its inactivation is usually total loss of one allele by deletion of whole chromosome 3 (monosomy 3) and somatic mutation impacting the other allele. In the following study we assessed the frequency of other potential mechanisms of biallelic inactivation of BAP1 in UM.
Approval for this project was obtained from the Institutional Review Board of the Ohio State University. Tumors from 17 patients were included. Protein expression was assessed by Western blot and/or by immunohistochemistry. Chromosomal status was assessed by microsatellite genotyping or molecular cytogenetics, and BAP1 mutational status by direct sequencing.
Table 1 summarizes our results.
This work shows that each technique has its own limitations to assess biallelic inactivation of BAP1, combination of multiple approaches is necessary for proper characterization of biallelic loss of BAP1. Non-genomic mechanisms for inactivation of BAP1 exist and need to be further explored. Large intragenic deletion of BAP1 is not rare and need to be considered when designing assays for detection of somatic mutation status of this gene.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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