title: BRAF mutations in multiple sebaceous hyperplasias of patients belonging to MYH-associated polyposis pedigrees.
abstract: The characteristics of sebaceous gland hyperplasia (SGH) consist of yellowish or skin-colored papules and nodules. Chronic sun exposure and immunosuppressed conditions are the main environmental risk factors, whereas chronological aging regulated by hormones and molecular changes are the intrinsic risk factors. We have evaluated the contribution of BRAF, K-Ras, and N-Ras mutations to the pathogenesis of SGHs in four patients belonging to three MYH-associated polyposis (MAP) pedigrees. MAP is an autosomal-recessive disease characterized by multiple colorectal adenomas and cancer. Immunohistochemistry of mismatch repair and APC proteins was performed. DNA isolated from blood lymphocytes and formalin-fixed or paraffin-embedded SGHs was PCR amplified and sequenced. In the SGH patients, we detected T1796A heterozygous substitution (V600E) in the BRAF gene. Compound biallelic germline MYH mutations (Y165C/G382D, R168H/379delC, and Y90X/delGGA464) were detected in the MAP patients. In contrast to the majority of melanocytic lesions, activating hotspot mutations in BRAF have not been involved so far in the pathogenesis of SGH. BRAF mutation is not a specific marker of melanocytic cancerogenesis, and it can also be involved in SGHs. In both melanocytic and non-melanocytic skin tumors, BRAF mutation is linked to early tumorigenesis events.
authors.affiliation: Department of Internal Medicine, Division of Dermatology, University of Modena and Reggio Emilia, Modena, Italy. ponti.giovanni@unimo.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ponti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Venesio
authors.forename: Lorena
authors.initials: L
authors.lastname: Losi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellacani
authors.forename: Lucio
authors.initials: L
authors.lastname: Bertario
authors.forename: Paola
authors.initials: P
authors.lastname: Sala
authors.forename: Monica
authors.initials: M
authors.lastname: Pedroni
authors.forename: Consalvo
authors.initials: C
authors.lastname: Petti
authors.forename: Stefania
authors.initials: S
authors.lastname: Maffei
authors.forename: Liliana
authors.initials: L
authors.lastname: Varesco
authors.forename: Erika
authors.initials: E
authors.lastname: Lerch
authors.forename: Andrea
authors.initials: A
authors.lastname: Baggio
authors.forename: Sara
authors.initials: S
authors.lastname: Bassoli
authors.forename: Caterina
authors.initials: C
authors.lastname: Longo
authors.forename: Stefania
authors.initials: S
authors.lastname: Seidenari
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000453:epidemiology* / Q000235:genetics* / Q000601:surgery; D000328:Adult; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012307:Risk Factors; D012625:Sebaceous Gland Diseases / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf