title: Loss of BAP1 Expression in Basal Cell Carcinomas in Patients With Germline BAP1 Mutations.
abstract: OBJECTIVE
  Patients with heterozygous germline mutations in BRCA1-associated protein 1 (BAP1), a tumor suppressor gene, develop a tumor predisposition syndrome (OMIM 614327) with increased risk of uveal and cutaneous melanomas, cutaneous atypical and epithelioid melanocytic lesions, lung adenocarcinoma, clear cell renal cell carcinoma, and other tumors. Early recognition of this syndrome is of clinical importance. In addition, screening for BAP1 mutation, loss, and inactivation by performing BAP1 immunohistochemistry on cutaneous lesions would be a simple method for screening patients suspected of having germline BAP1 mutations.
  
  
  METHODS
  We investigated BAP1 expression in seven basal cell carcinomas (BCCs) in two patients with germline BAP1 mutation and a family history of uveal melanoma. Six lesions were from the head and neck region and one from the shoulder. Thirty-one sporadic BCCs were included as controls.
  
  
  RESULTS
  All seven BCCs in the patients with germline BAP1 mutations exhibited loss of BAP1 nuclear staining, while 30 (97%) of 31 sporadic BCCs exhibited positive BAP1 nuclear staining.
  
  
  CONCLUSIONS
  Loss of BAP1 expression could be associated with the development of BCC in patients with germline BAP1 mutations. These results suggest that BCC may be a component of the expanding category of tumors associated with this syndrome.
authors.affiliation: From the Department of Pathology, Massachusetts General Hospital, Boston;
authors.forename: Mark C
authors.initials: MC
authors.lastname: Mochel
authors.affiliation: From the Department of Pathology, Massachusetts General Hospital, Boston; Department of Dermatology, Brigham and Women's Hospital, Boston, MA; and Harvard Medical School, Boston, MA.
authors.forename: Adriano
authors.initials: A
authors.lastname: Piris
authors.affiliation: From the Department of Pathology, Massachusetts General Hospital, Boston; Harvard Medical School, Boston, MA.
authors.forename: Vania
authors.initials: V
authors.lastname: Nose
authors.affiliation: From the Department of Pathology, Massachusetts General Hospital, Boston; Harvard Medical School, Boston, MA. mhoang@mgh.harvard.edu.
authors.forename: Mai P
authors.initials: MP
authors.lastname: Hoang
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D012878:Skin Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1; Basal cell carcinoma; Immunohistochemistry