A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid cancer

Cancer Genet. 2016 Mar;209(3):75-81. doi: 10.1016/j.cancergen.2015.12.007. Epub 2015 Dec 22.


Germline mutations in the tumor suppressor gene, BRCA-1 associated protein (BAP1), underlie a tumor predisposition syndrome characterized by increased risk for numerous cancers including uveal melanoma, melanocytic tumors and mesothelioma, among others. In the present study we report the identification of a novel germline BAP1 mutation, c.1777C>T, which produces a truncated BAP1 protein product and segregates with cancer. Family members with this mutation demonstrated a primary clinical phenotype of autosomal dominant, early-onset melanocytic neoplasms with immunohistochemistry (IHC) of these tumors demonstrating lack of BAP1 protein expression. In addition, family members harboring the BAP1 c.1777C>T germline mutation developed other neoplastic disease including thyroid cancer. IHC analysis of the thyroid cancer, as well, demonstrated loss of BAP1 protein expression. Our investigation identifies a new BAP1 mutation, further highlights the relevance of BAP1 as a clinically important tumor suppressor gene, and broadens the range of cancers associated with BAP1 inactivation. Further study will be required to understand the full scope of BAP1-associated neoplastic disease.

Keywords: BAP1; Cancer genetics; melanoma; thyroid cancer; tumor predisposition syndrome.

Publication types

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

MeSH terms

  • Female
  • Germ-Line Mutation*
  • Humans
  • Middle Aged
  • Nevus, Pigmented / genetics*
  • Skin Neoplasms / genetics*
  • Thyroid Neoplasms / genetics*
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / genetics*
  • Ubiquitin Thiolesterase / analysis
  • Ubiquitin Thiolesterase / genetics*


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