title: Multiple Cutaneous Melanomas and Clinically Atypical Moles in a Patient With a Novel Germline BAP1 Mutation.
abstract: OBJECTIVE
  Several kindreds having germline BAP1 mutations with a propensity for uveal and cutaneous melanomas and other internal malignancies have been described in an autosomal dominant tumor predisposition syndrome. However, clinically atypical moles have not been previously recognized as a component of this syndrome, to our knowledge. We describe the first kindred to date with a germline mutation in BAP1 associated with multiple cutaneous melanomas and classic dysplastic nevus syndrome.
  
  
  METHODS
  We describe a 53-year-old man who was initially seen in 2003 with dysplastic nevus syndrome, multiple atypical melanocytic proliferations showing loss of immunostaining for BAP1, and 7 cutaneous melanomas. Germline testing was performed in the proband, his 16-year-old son, and his 13-year-old daughter, revealing a germline mutation in the BAP1 gene (c.592G>T, p.Glu198X) in the proband and in his 16-year-old son. CDKN2A and CDK4 genes were wild type. No members of this kindred reported a history of uveal melanoma.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report of a patient with multiple melanomas, dysplastic nevus syndrome, and an inactivating germline BAP1 mutation. The coexistence of dysplastic nevus syndrome and a BAP1 germline mutation extends the spectrum of the BAP1 tumor predisposition syndrome and may confer a greater risk for cutaneous melanomas.
authors.affiliation: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois2Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Pedram
authors.initials: P
authors.lastname: Gerami
authors.affiliation: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Oriol
authors.initials: O
authors.lastname: Yélamos
authors.affiliation: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Christina Y
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Roxana
authors.initials: R
authors.lastname: Obregon
authors.affiliation: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Pedram
authors.initials: P
authors.lastname: Yazdan
authors.affiliation: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Sholl
authors.affiliation: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Gerta E
authors.initials: GE
authors.lastname: Guitart
authors.affiliation: Wellman Center for Photomedicine and Department of Dermatology, Massachusetts General Hospital, Harvard University, Boston4Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston.
authors.forename: Ching-Ni
authors.initials: CN
authors.lastname: Njauw
authors.affiliation: Wellman Center for Photomedicine and Department of Dermatology, Massachusetts General Hospital, Harvard University, Boston4Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston.
authors.forename: Hensin
authors.initials: H
authors.lastname: Tsao
mesh_terms: D000293:Adolescent; D004416:Dysplastic Nevus Syndrome / Q000235:genetics / Q000473:pathology*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D009506:Nevus / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase