Germline BAP1 mutation in a family with high incidence of multiple primary cancers and a potential gene-environment interaction

Cancer Lett. 2015 Dec 28;369(2):261-5. doi: 10.1016/j.canlet.2015.09.011. Epub 2015 Sep 26.

Abstract

We report a high-risk cancer family with multiple mesotheliomas, cutaneous melanomas, basal cell carcinomas, and meningiomas segregating with a germline nonsense mutation in BAP1 (c.1938T>A; p.Y646X). Notably, most (four of five) mesotheliomas were peritoneal rather than the usually more common pleural form of the disease, and all five mesothelioma patients also developed second or third primary cancers, including two with meningiomas. Another family member developed both cutaneous melanoma and breast cancer. Two family members had basal cell carcinomas, and six others had melanocytic tumors, including four cutaneous melanomas, one uveal melanoma, and one benign melanocytic tumor. The family resides in a subtropical area, and several members had suspected exposure to asbestos either occupationally or in the home. We hypothesize that the concurrence of a genetic predisposing factor and environmental exposure to asbestos and UV irradiation contributed to the high incidence of multiple cancers seen in this family, specifically mesothelioma and various uveal/skin tumors, respectively.

Keywords: Asbestos; BAP1; Cancer predisposition; Familial cancer; Malignant mesothelioma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asbestos / metabolism*
  • Disease Susceptibility
  • Gene-Environment Interaction
  • Germ-Line Mutation
  • Humans
  • Incidence
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Skin Neoplasms
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin Thiolesterase / genetics*
  • Ubiquitin Thiolesterase / metabolism

Substances

  • BAP1 protein, human
  • Tumor Suppressor Proteins
  • Asbestos
  • Ubiquitin Thiolesterase

Supplementary concepts

  • Melanoma, Cutaneous Malignant