Definition of a GCAT population panel for the Control of Mutations in Hereditary Cancer in the Catalan population
- Dra. Concepción Lázaro García
- Instituto de Investigación Biomédica de Bellvitge, HEREDITARY CANCER PROGRAM (ICO-IDIBELL)
Paula Rofes, Instituto de Investigación Biomédica de Bellvitge (IDIBELL)
Rafael de Cid, GenomesForLife-GCAT, PMPPC-Institut Germans Trias i Pujol (IGTP)
The current project requires the transfer of DNA to create an extensive population panel for the control of mutations in hereditary cancer in the Catalan population.
Massive sequencing technology for the complete analysis of the genetic sequence of patients allows rapid and comprehensive screening of mutational profiles with hereditary cancer. Although only with clinical validity in a defined set of variants, defined as risk mutations in broad international consensus, multiple other variants with pathogenic value not yet confirmed are generated in each new analysis. Validation by frequency in a population of the same geographic-ethnic origin is a common criterion used to assess its pathogenic level.
Given the prospective nature of the GCAT cohort, the characterization of new, undescribed variants entails an added value to the genomic characterization of the GCAT population cohort, relevant to its general objective.
At present, germline mutations have been described in more than 100 genes implicated in hereditary predisposition to cancer. Until recently, the study of hereditary cancer focused on the analysis of one or a few genes related to the phenotype observed in the patient / family. The application of massive sequencing technology (NGS) enables the study of multiple genes in a cost-effective way. However, today the phenotypes and risks associated with several of the genes / variants identified in patients with hereditary cancer are unknown.
Currently, massive sequencing technology is applied for the complete analysis of the genetic sequence of patients. Although only with clinical validity in a defined set of variants, defined as risk mutations in broad international consensus, multiple other variants with pathogenic value not yet contrasted are generated in each analysis. Mainly, there are data from large international consortia for hereditary colorectal cancer (CRC) and for hereditary breast and ovarian cancer (OHC), which allow defining the degree of pathogenicity of the genetic variants identified in the patients.
Genetic variants have a specific geographic-ethnic distribution. The study of the variants in a sample of the general population with the same geographic-ethnic distribution as the group of patients will allow us to discern the pathogenic role and better define the associated risk. The increase in the rate of genetic diagnosis of the studied population will improve the understanding of the genotype-phenotype relationships and associated risk.
Creation of a panel of samples for analysis of the frequency of the genetic variants identified with medium-low pathogenic value, which are identified during the process of genetic-clinical care analysis; in a large cohort of volunteers from the general population (n = 1500) of the same geographic-ethnic distribution as the patients.
Contact person: Dra. Conxi Lázaro