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Evaluation of the polymorphism of Fatty Acid Synthase (FASN) gene and of the lipogenesis in melanomas.

Abstract

Melanoma is a potentially aggressive tumor from melanocytic origin. The main affected region by this neoplasia is the skin, and the mucosa may be rarely affected. Generally, the pathogenesis of malignant neoplasias is characterized by a complex mixture of genetic and metabolic alterations. It is recognized that the metabolism of cancerous cell gives it advantages in survival. The increase in lipogenesis is a common phenotype in numerous human cancers and has been associated with differentiation, proliferation and tumoral agressiveness. It is believed that the superexpression of the enzyme responsible for the terminal catalytic phase in the synthesis of fatty acid (fatty acid synthase - FASN) is involved with the origin and progression of melanoma. The single nucleotide polymorphisms (SNPs) of FASN have been related in biological behavior and risk of developing some types of cancers, but in melanoma these SNPs have not yet been investigated . Intracytoplasmic lipid droplets (LDs), which may be detected by adipophilin expression, have been associated with several tumor phenotypes (growth, proliferation and stem cell marker), however in melanoma it has been only studied in culture cells. Considering these aspects, the objective of our study is to verify across a group of cutaneous and mucous melanoma, the relation between LDs, stem cells, cellular proliferation, FASN expression and neoplastic progression. Besides, the aim is to evaluate if FASN SNPs alter protein expression, risk, clinical manifestations, biological aspects and prognosis of cutaneous melanoma. (AU)

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