Protein-molecular profile of homologous recombination in the clinical evolution of gastric adenocarcinomas

Abstract

Gastric adenocarcinoma is a worldwide public health problem with a multifactorial etiology that involves genetic/epigenetic and environmental conditions. The development of cancer is characterized by a complex series of phenomena occurring at the level of DNA, including inadequate repair that generates accumulation of mutations and genetic instability, and epigenetic changes with aberrant methylation pattern and histone modifications. The double-strand break represents the greatest threat to DNA integrity, with homologous recombination (HR) being one of the main ways of repair. An extensive network of proteins is involved in HR to detect, signal and repair DNA damage. The functionally most important proteins are BRCA1, BRCA2, ATM, ATR, MDC1 and MRE11-RAD50-NBS1 complex, among others. The loss of BRCA1 and MDC1 expression has been indicated as a predictive factor in the development and progression of gastric tumor. The purpose of our study will be to evaluate the participation of homologous recombination associated with epigenetic changes in gastric cancers. We will perform analysis, in gastric adenocarcinomas, of the methylation of HR related genes (BRCA1, BRCA2, FEN1, MRE11A, RAD50, RAD51, ATM) through methylation-specific qPCR array in frozen samples and of the transcription of the same genes into mRNA through RT-qPCR array. We will also evaluate the expression of proteins related to HR (BRCA1, BRCA2, ATM, ATR, CHK2, ³H2AX, RAD51, p53) through immunohistochemistry in paraffin-embedded samples of the same cases of adenocarcinoma. (AU)