1. ¹Department of Internal Medicine, Division of Dermatology, University of Modena and Reggio Emilia, Modena, Italy
2. ²Division of Pathology, IRCC-Institute for Cancer Research and Treatment, Candiolo-Torino, Italy
3. ³Department of Pathology, University of Modena and Reggio Emilia, Modena, Italy
4. ⁴Italian Registry of Hereditary Colorectal Tumors, Department of Predictive and Preventive Medicine, National Cancer Institute, Milano, Italy
5. ⁵Department of Internal Medicine, Division of Medicine, University of Modena and Reggio Emilia, Modena, Italy
6. ⁶Hereditary Tumors Unit, National Cancer Institute, Genova, Italy
7. ⁷Oncology Institute of Southern Switzerland, Division of Medical Oncology, Bellinzona, Switzerland

Correspondence: Dr Giovanni Ponti, Department of Internal Medicine, Division of Dermatology, University of Modena and Reggio Emilia, Modena, via del Pozzo, Modena 41100, Italy. E-mail: ponti.giovanni@unimo.it

Received 10 July 2006; Revised 21 October 2006; Accepted 15 November 2006; Published online 1 February 2007.

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.