Exomes of ductal luminal breast cancer patients from southwest Colombia: Gene mutational profile and related expression alterations

This article belongs to the Special Issue Bioinformatics and Precision Computational Biology: Selected Papers from the X International Conference on Bioinformatics #SoIBio+10.Cancer is one of the leading causes of mortality worldwide. Breast cancer is the most frequent cancer in women, and in recent years it has become a serious public health problem in Colombia. The development of large-scale omic techniques allows simultaneous analysis of all active genes in tumor cells versus normal cells, providing new ways to discover the drivers of malignant transformations. Whole exome sequencing (WES) was obtained to provide a deep view of the mutational genomic profile in a set of cancer samples from Southwest Colombian women. WES was performed on 52 tumor samples from patients diagnosed with invasive breast cancer, which in most cases (33/52) were ductal luminal breast carcinomas (IDC-LM-BRCA). Global variant call was calculated, and six different algorithms were applied to filter out false positives and identify pathogenic variants. To compare and expand the somatic tumor variants found in the Colombian cohort, exome mutations and genome-wide expression alterations were detected in a larger set of tumor samples of the same breast cancer subtype from TCGA (that included DNA-seq and RNA-seq data). Genes with significant changes in both the mutational and expression profiles were identified, providing a set of genes and mutations associated with the etiology of ductal luminal breast cancer. This set included 19 single mutations identified as tumor driver mutations in 17 genes. Some of the genes (ATM, ERBB3, ESR1, TP53) are well-known cancer genes, while others (CBLB, PRPF8) presented driver mutations that had not been reported before. In the case of the CBLB gene, several mutations were identified in TCGA IDC-LM-BRCA samples associated with overexpression of this gene and repression of tumor suppressive activity of TGF-β pathway.This research was funded by Fondo de Investigación Sanitaria—Instituto de Salud Carlos III (FIS-ISCIII, Spanish Ministry of Health, project reference PI18/00591) where J.D.L.R. was the PI. The work within this project was also co-funded by the FEDER program of the European Union. The project on breast cancer from Colombia patients was funded by Sistema de Regalías del Valle del Cauca, Colombia (reference BPIN 2013000100297). P.A.M. acknowledges the Sistema de Regalías del Valle del Cauca, Colombia. J.D.L.R. also acknowledges the support given to his group by the European Project H2020 ArrestAD (Project ID: 737390, H2020-FETOPEN-1-2016-2017). C.C.-U. was supported by a graduate grant from COLCIENCIAS.Peer reviewe