Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population.
Cancers. 2022 Apr 20*** epublish ***
Rodrigo González-Barrios, Nicolás Alcaraz, Michel Montalvo-Casimiro, Alejandra Cervera, Cristian Arriaga-Canon, Paulina Munguia-Garza, Diego Hinojosa-Ugarte, Nora Sobrevilla-Moreno, Karla Torres-Arciga, Julia Mendoza-Perez, José Diaz-Chavez, Carlo Cesar Cortes-González, Clementina Castro-Hernández, Jorge Martínez-Cedillo, Ana Scavuzzo, Delia Pérez-Montiel, Miguel A Jiménez-Ríos, Luis A Herrera
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Mexico City 14080, Mexico., Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Instituto Nacional de Medicina Genómica, Mexico City 14610, Mexico., Departamento de Cirugía, Hospital Regional de Alta Especialidad del Bajío, Leon 37660, Mexico., Departamento de Oncología Médica, Clínica de Tumores Genitourinarios, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Departamento de Urología, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., Departamento de Patología, Instituto Nacional de Cancerología, Mexico City 14080, Mexico.