Abstract 335: Mutation analysis of KRAS and BRAF genes in sebaceous lesions and keratoacanthomas sporadic or related to hereditary syndrome

BACKGROUND: Sebaceous lesions comprises: hyperplasias, adenomas, sebaceomas and carcinomas, which can be sporadic or related to hereditary syndrome. Keratoacanthomas, as sebaceous lesions, can be associated with hereditary cancer, known as Muir-Torre syndrome (MTS), accepted as the presence of those lesions with visceral malignancies, mainly colorectal cancer (CRC). Besides, a subset of MTS shares clinical, pathological and molecular characteristics with hereditary nonpolyposis colorectal cancer (HNPCC). BRAF mutation has already been described in sebaceous hyperplasia but not in CRC in an onset of HNPCC. BRAF oncogene is part of the MAPKinase pathway, as KRAS gene, and both have an important role in cellular proliferation, differentiation and apoptosis. OBJECTIVE: The aim of this study was to evaluate the role of KRAS and BRAF genes in sebaceous lesions and keratoacanthomas in a sporadic setting or related with hereditary syndrome. METHODS: KRAS (codons 12 and 13) and BRAF (V600E) mutations of 52 sebaceous lesions and 42 keratoacanthomas samples was evaluated using Sanger sequencing. 24 (46%) patients had at least one internal malignancy and thus were diagnosed as having MTS. 7 (14%) patients presented clinical or molecular diagnosis of HNPCC. RESULTS: Mutations in KRAS was identified in 7 of 52 cases (14%) of sebaceous lesions and 10 of 42 cases (24%) of keratoacanthomas. BRAF mutation was observed in 2 of 52 cases (4%) of sebaceous lesions and 2 of 42 cases (5%) of Keratoacanthomas. Mutation in both genes occurred in just one sample. There was no statistical significance observed with clinical variables. BRAF mutation was not observed in patients with diagnosis of MTS or HNPCC. CONCLUSION: The results indicate that KRAS and BRAF mutations play a distinct role in carcinogenesis of sebaceous lesions and KRAS a more important event in keratoacanthomas. KRAS mutation was observed in sporadic lesions and also related to hereditary syndrome. However, BRAF mutation was not observed in patients with HNPCC, concordant with observed in CRC with the same origin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 335. doi:10.1158/1538-7445.AM2011-335