title: Germline BAP1 mutations predispose also to multiple basal cell carcinomas.
abstract: The BRCA1-associated protein 1 (BAP1) gene encodes a nuclear deubiquitin enzyme which acts as a tumour suppressor. Loss of function germline mutations of BAP1 have been associated with an enhanced risk of uveal and cutaneous melanomas, mesothelioma, clear cell renal cancer and atypical cutaneous melanocytic proliferations. In two independent BAP1 families, we noticed an unusual frequency of basal cell carcinomas (BCCs). Indeed, 19 BCCs were diagnosed in four patients, either of superficial (13/19) or nodular (6/19) subtype; they were all located in chronic sun-exposed areas (limbs, head or neck). Immunohistochemistry (IHC) identified in the 19 tumours, complete or partial loss of BAP1 protein nuclear expression, restricted to the BCC nests. A control study was conducted in 22 sporadic BCCs in 22 subjects under 65 without known associated BAP1 tumours: no loss of BAP1 expression was found. Overall, our observations suggest that BCCs are part of the BAP1 cancer syndrome, perhaps in relation with chronic sun exposure and melanocortin 1 receptor (MC1R) variants. In conclusion, cutaneous follow-up of BAP1 carriers should not only aim to detect melanocytic neoplasms but also BCCs.
authors: Département de Biopathologie, Centre Leon Bérard, Lyon, France.
authors: A
authors: http://orcid.org/0000-0003-2251-8241
authors: A
authors: de la Fouchardière
authors: Gustave Roussy, Service de Génétique, Villejuif, France.
authors: O
authors: O
authors: Cabaret
authors: Service de Dermatologie, Polyclinique de Courlancy, Reims, France.
authors: L
authors: L
authors: Savin
authors: Service d'Onco-dermatologie, Centre Leon Bérard, Lyon, France.
authors: P
authors: P
authors: Combemale
authors: Cabinet de Pathologie, Pathologie, Reims, France.
authors: H
authors: H
authors: Schvartz
authors: Service d'Oncogénétique, Institut du Cancer Courlancy, Reims, France.
authors: C
authors: C
authors: Penet
authors: Service de Génétique, Centre Leon Bérard, Lyon, France.
authors: V
authors: V
authors: Bonadona
authors: Service de Génétique, Hôpital Bichat Claude Bernard, INSERM U976, Paris, France.
authors: N
authors: N
authors: Soufir
authors: Gustave Roussy, Service de Génétique, Villejuif, France.
authors: B
authors: B
authors: Bressac-de Paillerets
mesh_terms: D000328:Adult; D002280:Basal Cell Carcinoma / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D044102:Receptor, Melanocortin, Type 1; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism
chemical_list: C400134:BAP1 protein, human; D044102:Receptor, Melanocortin, Type 1; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1 cancer syndrome; basal cell carcinoma; genetics; skin cancer