A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma

Clin Genet. 2015 Sep;88(3):267-72. doi: 10.1111/cge.12501. Epub 2014 Nov 6.


We report four previously undescribed families with germline BRCA1-associated protein-1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family.

Keywords: BAP1; BCC; cancer predisposition syndrome; germline mutation; melanoma; unknown primary tumor.

Publication types

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

MeSH terms

  • Carcinoma, Basal Cell / genetics*
  • Carcinoma, Basal Cell / metabolism
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation*
  • Haplotypes
  • Heterozygote
  • Humans
  • Loss of Heterozygosity
  • Male
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin Thiolesterase / genetics*
  • Ubiquitin Thiolesterase / metabolism


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