Comparative genome hybridization (CGH) and epigenetic regulation in neoplasms, in Alzheimer's Disease (DA) and in aging

• Grant number: 05/58988-5
• Support Opportunities: Regular Research Grants
• Duration: June 01, 2006 - May 31, 2008
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marilia de Arruda Cardoso Smith
• Grantee: Marilia de Arruda Cardoso Smith
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The Project is composed by four inter-related subprojects. I. Comparative Genome Hybridization (CGH) in gastric adenocarcinoma in Estado do Para population - Gastric cancer is one of the most frequent type of neoplasm and one of the main causes of death. In Para State, Brazil, it is a great problem of public health. Tumor samples will be investigated using CGH technique aiming to establish a chromosomal model for clone evolution. This technique has been successfully used in our laboratory and preliminary results showed 8 chromosome tiresome and C-MYC amplification in this gastric cancer. II. Epigenetic regulation in gastric adenocarcinoma - Epigenetic factors, such as DNA methylation, have been identified in normal and tumor differentiation processes in organism. Methylation frequency of CpG Island from promoter region genes potentially relevants for carcinogenesis will be investigated in 90 adenocarcinoma samples from Pará population using MSP (Methylation Specific PCR) technique aiming to associate the methylation pattern with cancer development. III. Epigenetic regulation and gene expression in renal tumors - Methylation process is also involved in genomic imprinting. Imprinted genes H19 and IGF2, will be investigated concerning their mono or biallelic expression using RT-PCR in 30 renal tumor samples from informative heterozygous subjects identified by specific polymorphisms. IV. Epigenetic regulation in Alzheimer disease (DA) and aging - Methylation frequency in c.pG Island from promoter regions of potentially relevant genes such as HTERT, P66SHC and genes involved in rDNA activity will be investigated in 40 patients with Alzheimer disease, 40 elderly and 40 young controls and will also be associated with rDNA expression. In our laboratory we observed originally a significant decrease of rDNA expression in DA. The used techniques will be MSP and slot dot for 28S and 18S RNA fractions quantification analysis. (AU)