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Retroelements in primary and metastatic colorectal tumors

Grant number: 15/25020-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2016
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Pedro Alexandre Favoretto Galante
Grantee:Fernanda Orpinelli Ramos Do Rego
Home Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil
Associated scholarship(s):17/23575-0 - A comprehensive study of novel Alu insertions in cancer, BE.EP.DR

Abstract

Colorectal cancer (CRC) is the third most common cancer in the world, with nearly 1 million new cases annually diagnosed. Of these, about 50% of the patients evolve to death mainly due to the development of secondary tumors, metastatic, originated from primary colorectal tumors. Thus, studying genetic variations in secondary tumors is central to understand better tumor progression and to provide treatments that are more effective to CRC-affected patients. In this Ph.D. project, we will develop and use bioinformatics methodologies, add next-generation DNA sequencing data, information about gene expression and epigenetics to study genomic variation present in primary and secondary tumors of CRC. Among genomic variations, we will develop methods to identify and evaluate the functional role from those caused by retrocopies of protein-coding genes and Alus, two types of unexplored genomic variations with great potential to be functional. As results, we expect, in a new way, to be the first group to catalog somatic events of protein-coding gene retrocopies and Alus in CRC secondary tumors (metastatic). We also intend to be pioneers in systematic investigation of possible causal relation between the occurrences of variations, generated by retroelements, and tumorigenesis for CRC. Thereby, our work aims to investigate two types of variations poorly studied, mostly in secondary tumors, and contribute to an understanding of the frequency and importance of these variations in tumorigenesis and metastasis of a very relevant type of cancer, the colorectal cancer.