IMTIB   27019
INSTITUTO DE MEDICINA TRASLACIONAL E INGENIERIA BIOMEDICA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Identification of the predisposing genetic variant for inherited colorectal cancer syndromes in Argentina
Autor/es:
BELEN CERLIANI; MARIANA CORAGLIO; PÄIVI PELTOMÄKI ; WALTER PAVICIC ; JONATHAN ZAIAT; ROMINA CAJAL; ALEJANDRO GUTIÉRREZ ; MARCELO MARTI ; ADRIÁN TURJANSKI ; MAYORDOMO, ANDREA CONSTANZA; TAMARA PIÑERO; KARINA COLLIA ÁVILA ; CARLOS VACCARO ; JAVIER I. MURILLO
Lugar:
Ciudad Autonoma de Buenos Aires
Reunión:
Congreso; 1st Congress of Women in Bioinformatics and Data Science LA 2020; 2020
Resumen:
Colorectal cancer (CRC) is one of the most common cancers worldwide. About 5-10% of all CRC are caused by a heritable germline genetic alteration. One of the two major subtypes of inherited CRC syndromes is Familial Adenomatous Polyposis (FAP). We aimed to identify novel genetic variants in 21 unrelated probands from Argentina with FAP syndromes (recruited at Hosp. Udaondo). Samples were first analyzed by Sanger sequencing (APC gene screening). Cases without an identified genetic defect were subsequently evaluated by whole-exome sequencing (WES). We identified pathogenic variants in 57% of individuals and included well-known genes such as APC (6/7 were novel), MUTHY, SMAD4, BMPR1A, and MSH6. Moreover, we identified five cases carrying a potentially causative variant in genes that could predispose to the inherited polyposis disorder, such as NUDT7, MUC17, E2F8, and OBSCN. These need to be analyzed at a functional level to get further insights into their biological role. Looking to identify genes that could play a role in disease symptomatology, we perform a preliminary statistical analysis by evaluating WES-derived data and associated metadata -clinical and molecular- from 16 individuals (as a positive control, we included in the analysis a sample from a Lynch-like proband). Results from PCAmix (RStudio) only explain 14.9% (accumulated) of the variability between the samples taking the first 4 dimensions. We observed that a specific group of genes (carrying potentially pathogenic variant), and with a suspected secondary role in cancer development, was shared by patients showing similar clinical features. To validate these preliminary results, extra samples need to be evaluated. In this study, we were able to identify variants that predispose to FAP and describe an exploratory data analysis approach useful to find a correlation between genetic and clinical features, which would allow us to understand the wide variety of symptoms in this pathology.