September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Mechanisms of somatic biallelic inactivation of BAP1 in uveal melanoma
Author Affiliations & Notes
  • Timothy W Grosel
    Department of Ophthalmology and Visual Science, Havener Eye Institute, The Ohio State University, Columbus, Ohio, United States
  • Getachew Boru
    Department of Ophthalmology and Visual Science, Havener Eye Institute, The Ohio State University, Columbus, Ohio, United States
  • James Massengill
    Department of Ophthalmology and Visual Science, Havener Eye Institute, The Ohio State University, Columbus, Ohio, United States
  • Frederick H Davidorf
    Department of Ophthalmology and Visual Science, Havener Eye Institute, The Ohio State University, Columbus, Ohio, United States
  • Colleen M Cebulla
    Department of Ophthalmology and Visual Science, Havener Eye Institute, The Ohio State University, Columbus, Ohio, United States
  • Mohamed H Abdel-Rahman
    Department of Ophthalmology and Visual Science, Havener Eye Institute, The Ohio State University, Columbus, Ohio, United States
    Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States
  • Footnotes
    Commercial Relationships   Timothy Grosel, None; Getachew Boru, None; James Massengill, None; Frederick Davidorf, None; Colleen Cebulla, None; Mohamed Abdel-Rahman, None
  • Footnotes
    Support  This work was supported by the Patti Blow Research Fund in Ophthalmology, funding from the Ohio Lions Eye Research Foundation, the R21CA191943 Grant from the National Cancer Institute (PI: Abdel-Rahman, MH), and the National Eye Institute grant K08EY022672 (CMC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, National Cancer Institute, or National Eye Institute.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5895. doi:
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    • Get Citation

      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : 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.

Methods : 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.

Results : Table 1 summarizes our results.

Conclusions : 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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