BRAF mutations in multiple sebaceous hyperplasias of patients belonging to MYH-associated polyposis pedigrees.
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.
Ponti
Giovanni
G
Department of Internal Medicine, Division of Dermatology, University of Modena and Reggio Emilia, Modena, Italy. ponti.giovanni@unimo.it
Venesio
Tiziana
T
Losi
Lorena
L
Pellacani
Giovanni
G
Bertario
Lucio
L
Sala
Paola
P
Pedroni
Monica
M
Petti
Consalvo
C
Maffei
Stefania
S
Varesco
Liliana
L
Lerch
Erika
E
Baggio
Andrea
A
Bassoli
Sara
S
Longo
Caterina
C
Seidenari
Stefania
S
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
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf