IDENTIFICATION OF THE PREDISPOSING GENETIC VARIANT FOR INHERITED COLORECTAL CANCER SYNDROMES IN ARGENTINA

MAYORDOMO, ANDREA CONSTANZA; PIÑERO, TAMARA; COLLIA AVILA, KARINA; MARTI, MARCELO; TURJANSKI, ADRIÁN; CERLIANI, MARÍA BELÉN; CORAGLIO, MARIANA; VACCARO, CARLOS; MURILLO, JAVIER; ZAIAT, JONATHAN; CAJAL, ANDREA; GUTIÉRREZ, ALEJANDRO; PAVICIC, WALTER

Congreso; 1st Congress of Women in Bioinformatics and Data Science Latin America; 2020

Colorectal cancer (CRC) is one of the most common cancers worldwide. About 5-10% of all CRCare caused by a heritable germline genetic alteration. One of the two major subtypes of inheritedCRC syndromes is Familial Adenomatous Polyposis (FAP). We aimed to identify novel geneticvariants in 21 unrelated probands from Argentina with FAP syndromes (recruited at Hosp.Udaondo). Samples were first analyzed by Sanger sequencing (APC gene screening). Caseswithout 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 suchas APC (6/7 were novel), MUTHY, SMAD4, BMPR1A, and MSH6. Moreover, we identified fivecases carrying a potentially causative variant in genes that could predispose to the inheritedpolyposis disorder, such as NUDT7, MUC17, E2F8 and OBSCN. These need to be analyzed at afunctional level to get further insights into their biological role. Looking to identify genes that couldplay a role in disease symptomatology, we perform a preliminary statistical analysis by evaluatingWES derived data and associated metadata -clinical and molecular- from 16 individuals (as apositive control, we included in the analysis a sample from a Lynch-like proband). Results fromPCAmix (RStudio) only explain 14.9% (accumulated) of the variability between the samples takingthe first 4 dimensions. We observed that a specific group of genes (carrying potentially pathogenicvariant), and with a suspected secondary role in cancer development, was shared by patientsshowing similar clinical features. To validate these preliminary results, extra samples need to beevaluated. In this study, we were able to identify variants that predispose to FAP, and describe anexploratory 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.