Molecular characterization of non-small cell lung cancer tumors in Latin American patients from Brazil, Chile and Peru uncovers novel potentially driver mutations

Sepulveda, Gonzalo; Blanco, Alejandro; Freire, Matías; Lizana, Rodrigo; Cáceres-Molina Javier; Ampuero, Diego; Pérez, Paola; Ramos, Liliana; Aren, Osvaldo; Chernilo, Sara; Spencer, María Loreto; Flores, Jacqueline; Bernal, Giuliano; Ahumanda, Mónica; Rasse, German; et. al.


ntroduction Therapies that target activating Egfr, Alk, Ros1 and other mutations have become first-line treatments that improve NSCLC patient life expectancy. Latin-American patients are poorly represented in clinical trials and in genomic databases, thus little is known about the prevalence of actionable mutations in this population. This study characterizes, for the first time, the somatic mutations found in 52 actionable genes, and describe a novel set of potentially actionable mutations, in NSCLC patients from Chile, Brazil and Peru, while correlating these genomic occurrences with relevant clinical, demographic and pathology aspects. Methods 1732 subjects diagnosed with NSCLC were analyzed. DNA and RNA were sequenced using a 52 genes NGS panel. Mutations were annotated using the Variant Effect Predictor, COSMIC, OncoKB and the Cancer Genome Interpreter to categorize somatic mutations. Results We found a total of 1713 mutations with 626 (36.5%) novel, potentially driver mutations. 66.1% of these novel mutations were predicted as Tier 1 driver mutations. Actionable mutations for Ret and Alk were more prevalent in Brazil than in Chile, whereas Met exon-14 skipping was significantly enriched in Chile. In Peru, Egfr is higher while Kras is lower. A high number of novels potentially driver mutations in know NSCLC actionable genes, such as Alk, Erbb2, Ret, Met, and Ros1, was found. Conclusions The analysis of many Latin America subjects revealed a significant number of clinically actionable but also novel somatic mutations in cancer genes highlighting the importance of including less-represented populations in clinical trials and molecular studies.

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Título de la Revista: medRxiv, the pre-print server for Health Sciences
Editorial: Cold Spring Harbor Laboratory
Fecha de publicación: 2020
Financiamiento/Sponsor: CEMP, Pfizer

DOI: 10.1101/2020.09.11.20171025