title: A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid cancer.
abstract: 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.
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: McDonnell
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Gallanis
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Heller
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Marilena
authors.initials: M
authors.lastname: Melas
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Idos
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Julie O
authors.initials: JO
authors.lastname: Culver
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Keck School of Medicine, Department of Pathology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Sue-Ellen
authors.initials: SE
authors.lastname: Martin
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Peng
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. Electronic address: sgruber@med.usc.edu.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
mesh_terms: D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000032:analysis / Q000235:genetics*
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1; Cancer genetics; melanoma; thyroid cancer; tumor predisposition syndrome