Genomic profile in TGCT Mexican patients reveals a potential biomarker of sensitivity to platinum-based therapy

Abstract

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, SNV and CNV signatures. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplification of 2q11.1 as a novel variant with chemosensitivity biomarker potential. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. Our data sheds light into understanding platinum resistance in a poorly characterized population.