title: Germline BAP1 mutation in a family with high incidence of multiple primary cancers and a potential gene-environment interaction.
abstract: We report a high-risk cancer family with multiple mesotheliomas, cutaneous melanomas, basal cell carcinomas, and meningiomas segregating with a germline nonsense mutation in BAP1 (c.1938T>A; p.Y646X). Notably, most (four of five) mesotheliomas were peritoneal rather than the usually more common pleural form of the disease, and all five mesothelioma patients also developed second or third primary cancers, including two with meningiomas. Another family member developed both cutaneous melanoma and breast cancer. Two family members had basal cell carcinomas, and six others had melanocytic tumors, including four cutaneous melanomas, one uveal melanoma, and one benign melanocytic tumor. The family resides in a subtropical area, and several members had suspected exposure to asbestos either occupationally or in the home. We hypothesize that the concurrence of a genetic predisposing factor and environmental exposure to asbestos and UV irradiation contributed to the high incidence of multiple cancers seen in this family, specifically mesothelioma and various uveal/skin tumors, respectively.
authors.affiliation: Cancer Biology Program and Genomics Facility, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Cheung
authors.affiliation: Cancer Biology Program and Genomics Facility, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Yuwaraj
authors.initials: Y
authors.lastname: Kadariya
authors.affiliation: Cancer Biology Program and Genomics Facility, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Talarchek
authors.affiliation: Cancer Biology Program and Genomics Facility, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Pei
authors.affiliation: Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1054, USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Ohar
authors.affiliation: University of Florida Health Cancer Center at Orlando Health, Orlando, FL 32806, USA.
authors.forename: Omar R
authors.initials: OR
authors.lastname: Kayaleh
authors.affiliation: Cancer Biology Program and Genomics Facility, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Electronic address: joseph.testa@fccc.edu.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Testa
mesh_terms: D001194:Asbestos / Q000378:metabolism*; D004198:Disease Susceptibility; D059647:Gene-Environment Interaction; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism; D000096142:Cutaneous Malignant Melanoma
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D001194:Asbestos; D043222:Ubiquitin Thiolesterase
keywords: Asbestos; BAP1; Cancer predisposition; Familial cancer; Malignant mesothelioma