Characterization Of The Expression Profile Of APOBEC And TET Families In Esophageal Squamous Cell Carcinoma

Marina NICOLAU, Instituto Nacional de Câncer, Brazil
NETO P. 1 , SIMÃO T. 2 , PINTO L. 1 , LIMA S. 1

1 Programa de Carcinogênese Molecular. Instituto Nacional de Câncer, Rio de Janeiro, Brazil
2 Departamento de Bioquímica, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

Esophageal squamous cell carcinoma (ESCC) is one of the main histological types of esophageal cancer worldwide and in Brazil. Although its high incidence and mortality rates, the mechanisms that lead to ESCC development are still poorly understood. Our group has shown before that alterations of DNA methylation are a common event in ESCC and may preceed the first genetic alterations, however what leads to this deregulation is still unkown. The specific pattern of DNA methylation depends on the balance between methylation and demethylation processes. We have shown that ESCC shows an overexpression of DNMT3B in comparison with normal surrounding mucosa, but genes from the demethylation machinery were not evaluated. More recently, APOBEC proteins (cytosine deaminases), related to the generation of genetic variability, have been implicated also in active DNA demethylation as well as TET proteins, which are involved in the hydroxylation of 5-methylcytosine. However, data regarding expression and regulation of APOBEC and TET families in ESCC is limited. Therefore, the aim of this study is to evaluate the expression profile of APOBECs and TETs and their regulation in ESCC patients. We analyzed the expression of these genes in tumor and matched surrounding normal tissue from up to 18 ESCC patients by RT-qPCR. APOBEC3A1, APOBEC3B, APOBEC3D, APOBEC3FA and APOBEC3G were found overexpressed in ESCC when compared with matched surrounding mucosa whereas TET2 was found downregulated. Additionally, APOBEC3B was able to distinguish surrounding mucosa from tumor with 94.44% sensitivity and 100% specificity while APOBEC3D distinguished theses two tissues with 88.89% sensitivity and the same specificity.  Our results suggest that the deregulation of the APOBEC family of genes is a common feature in ESCC and could be involved in the aberrant methylation profile previously observed. Funding source: Ministério da Saúde, FAPERJ.