Further Evidence for Germline BAP1 Mutations Predisposing to Melanoma and Malignant Mesothelioma

Cancer Genet. 2013 May;206(5):206-10. doi: 10.1016/j.cancergen.2013.05.018.

Abstract

We describe a new family with a novel germline BAP1 nonsense mutation, c.723T>G, which leads to a predicted truncated protein, p.Y241*, or nonsense-mediated decay of the BAP1 mRNA. The proband had uveal melanoma (UM), and his paternal family has a remarkable history of multiple cancers. The proband's father had both pleural malignant mesothelioma (MM) and cutaneous melanoma (CM); a paternal uncle had lung cancer, CM, and UM; and a grandmother had CM. The findings in this family provide further support for the existence of a BAP1 cancer syndrome that predisposes to MM, various melanocytic neoplasms, and potentially other cancers. The fact that several members of the family manifested two or more different types of cancer suggests widespread BAP1-related tumor susceptibility targeting tissues of multiple organs. In addition, a review of BAP1 cancer syndrome families reported to date indicates that the location of the BAP1 mutation does not have any bearing on the spectrum of cancer types observed, either for mesothelial or melanocytic tumors.

Keywords: BAP1; cancer susceptibility; cutaneous melanoma; mesothelioma; uveal melanoma.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Codon, Nonsense*
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation*
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Melanoma / genetics*
  • Mesothelioma / genetics*
  • Pedigree
  • RNA Stability / genetics
  • Tumor Suppressor Proteins / genetics*
  • Ubiquitin Thiolesterase / genetics*

Substances

  • BAP1 protein, human
  • Codon, Nonsense
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase

Supplementary concepts

  • Mesothelioma, Malignant