Abstract 3944: Base excision repair and gene expression profiling in malignant melanoma

Abstract

Abstract Melanoma is a potentially deadly skin tumour and its incidence continues to increase worldwide. Despite the many efforts to elucidate the molecular mechanisms involved in melanoma development, these pathways still remain relatively unknown. For this reason, new methods are required to identify new biological targets implicated in melanoma. Our pilot study examined whole genome gene expression (Illumina Ref8 V2) in 82 melanoma samples and 8 control melanocyte cell lines. Gene transcripts with significantly altered expression (p<0.05) and greater than 2-fold change were identified for the melanomas compared to the melanocytes (GeneSpring GX V10), revealing a number of new targets not previously described in melanoma. Interestingly, a number of genes involved in the DNA repair, immune response and cell cycle arrest pathways were differentially expressed in the melanomas. With respect to the DNA repair pathways, we identified that key components of the base excision repair (BER) pathway were significantly altered in melanoma. Sequencing analysis confirmed several alterations in genes involved in the BER pathway and the frequency of these variants were further confirmed in an independent cohort of 105 formalin-fixed paraffin embedded (FFPE) melanoma patients. Hierarchical cluster analysis showed that melanoma patients with sequence variants in the BER pathway had altered gene expression profiles compared to those melanoma patients with no known variants in this pathway. Taken together, these results suggest that the BER pathway may be implicated in the development of melanoma, which may lead to the introduction of mutation screening and gene expression profiling for the management of melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3944.