Abstract
Abstract Cancers arise due to accumulation of mutations in genes critical for cell proliferation, differentiation, and cell death. Direct interaction with cell cycle regulators characterizes growth suppression by several tumor suppressor genes. Mutation or polymorphisms that occur in the promoter or coding regions may affect gene expression and may thus have the potential to be of phenotypic or even of pathological significance. In our previous studies, we showed the differential gene expression patterns and gene interactions/ association of of BCCIP and/or CDKN2A gene1, TNF and/or CCR52 with respect to genotypes, melanoma types and family history. We reported a significant interaction between BCCIP and CDKN2A genotypes among melanoma cases and a significant difference between cases and controls for the BCCIP/CDKN2A haplotype, when adjusted with age and sex, possibly confering different levels of susceptibility to melanoma. In the same report we also had a finding of CDKN2A mutant genotype showing significant association with Melanoma type 1 followed by type 2 suggesting this gene to be critical only in cases with family history and /or with other malignancy. Previous reports have shown that BCCIP as an important component in maintaining the tumor suppression function of wild type p53.Without BCCIP, p53 fails to form tetramers, cannot bind with its target promoter sequences, and is defective in transactivation activity. The p53 pathway responds to cellular stresses that threaten the fidelity of DNA replication, genome stability, chromosome separation and cell division. Many of the cellular stresses can be oncogenic in nature and in skin, the most damaging stresses in carcinogenesis is UV radiation. In this follow up study we show a strong association of p53 codon72 polymorphism (p<0.003) with melanoma (N=126) as compared to controls (N=172). Positive correlations of p53 gene with BCCIP polymorphism (p<.013), BCCIP(p<0.010) & CDKN2A(p<0.032) gene expressions from tumor tissues from melanoma patients suggest the possible functional role of these reported gene interactions in causation or in disease progression. A 12 gene panel (TNF, CCR5 and other CDK pathway genes) and their possible interactions showing clinical relevance of these markers in melanoma development and/or progression through p53-dependent mechanism are discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2651. doi:1538-7445.AM2012-2651
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