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Genomic Profile in a Non-Seminoma Testicular Germ-Cell Tumor Cohort Reveals a Potential Biomarker of Sensitivity to Platinum-Based Therapy

SIMPLE SUMMARY: Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Incidence and mortality of this disease has remained unchanged in Latin populations unlike the rest of the world. To date, the search for g...

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Detalles Bibliográficos
Autores principales: González-Barrios, Rodrigo, Alcaraz, Nicolás, Montalvo-Casimiro, Michel, Cervera, Alejandra, Arriaga-Canon, Cristian, Munguia-Garza, Paulina, Hinojosa-Ugarte, Diego, Sobrevilla-Moreno, Nora, Torres-Arciga, Karla, Mendoza-Perez, Julia, Diaz-Chavez, José, Cortes-González, Carlo Cesar, Castro-Hernández, Clementina, Martínez-Cedillo, Jorge, Scavuzzo, Ana, Pérez-Montiel, Delia, Jiménez-Ríos, Miguel A., Herrera, Luis A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101377/
https://www.ncbi.nlm.nih.gov/pubmed/35565196
http://dx.doi.org/10.3390/cancers14092065
Descripción
Sumario:SIMPLE SUMMARY: Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Incidence and mortality of this disease has remained unchanged in Latin populations unlike the rest of the world. To date, the search for genetic variants in our population remains unexplored. The aim of this study is to identify predictive biomarkers of resistance to platinum-based therapy, whether general or specific to the Latin population. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. However, we identified 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. 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, 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.