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Pancreatic ductal adenocarcinomas from Mexican patients present a distinct genomic mutational pattern

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in humans, with less than 5% 5-year survival rate. PDAC is characterized by a small number of recurrent mutations, including KRAS, CDKN2A, TP53, and SMAD4 and a long “tail” of infrequent mutated genes. Most of the studies have been performed in US and European populations, so new studies are needed to describe the mutational landscape of these tumors in other cohorts. The present study analyzed the exome and transcriptome of four PDAC tumors from Mexican patients. We found a paucity of the previously described recurrent mutations, with mutations in only three genes (HERC2, CNTNAP2 and HMCN1) previously reported in PDAC with a frequency > 1%. In addition, we discovered several recurrent putative copy number aberrations in SKP2, BRAF, CSSF1R, FOXE1, JAK2 and MET genes and in genes previously reported as putative drivers in PDAC, including KRAS, SF3B1, BRAF, MYC and MET. Although a larger cohort is needed to validate these findings, our results could be pointing toward potential differences in contributing factors for PDAC in Latin-American populations.

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Funding

Paulina Sanchez is a Doctoral Student from Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), and received a Fellowship 397501 from CONACyT. Rodrigo Barquera is a Doctoral Student funded by the Max Planck Institute for the Science of Human History in Jena, Germany. This work was supported by Consejo Nacional de Ciencia y Tecnologia (CONACyT) Grant Number 2011-CO1-161619.

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Author notes

  1. Adrian Cravioto

    Present address: Cirugia Oncologica, Centro Medico ABC, Santa Fe, Mexico, Mexico

Authors and Affiliations

  1. Functional Genomics Laboratory, Medical Research Subdirection, Instituto Nacional de Medicina Genomica, Periferico Sur 4809, Tlalpan, Arenal Tepepan, 14610, Mexico, Mexico

    Paulina Sanchez, Magali Espinosa & Jorge Melendez-Zajgla

  2. Epigenetics Laboratory, Basic Research Subdirection, Instituto Nacional de Medicina Genomica, Periferico Sur 4809, Tlalpan, Arenal Tepepan, 14610, Mexico, Mexico

    Vilma Maldonado

  3. Department of Archaeogenetics, Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745, Jena, Germany

    Rodrigo Barquera

  4. Pathology Department, Instituto Nacional de Medicina Genomica, Periferico Sur 4809, Tlalpan, Arenal Tepepan, 14610, Mexico, Mexico

    Nayeli Belem-Gabiño

  5. Unidad de Investigacion en Enfermedades Infecciosas y Parasitarias, Centro Medico Nacional Siglo XXI, IMSS, Mexico, Mexico

    Javier Torres

  6. Hospital de Especialidades, Centro Medico Nacional Siglo XXI, IMSS, Mexico, Mexico

    Adrian Cravioto

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  1. Paulina Sanchez
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Contributions

PS performed experiments and data analysis. ME performed experiments. RB performed the ancestry analyses. VM integrated results and drafted the manuscript. NBG performed pathologic assessments. JT and AC performed clinical analyses, helped collect the samples and obtained the clinical information. JM-Z performed data analysis, designed the study, integrated the results and drafted the manuscript.

Corresponding author

Correspondence to Jorge Melendez-Zajgla.

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The authors declare no competing financial interests.

Ethical approval

The project was approved by Instituto Nacional de Medicina Genomica’s (INMEGEN) Ethical, Biosecurity and Scientific Committees, by the Scientific Committee of Instituto Mexicano del Seguro Social (IMSS) and by Mexico’s Federal Health Regulation Office COFEPRIS (Comision Federal para la Proteccion contra Riesgos Sanitarios, project Genomica del Cancer. Capitulo Mexico CMN2011-020). All procedures were performed according to the guidelines and regulations approved by these Committees.

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Sanchez, P., Espinosa, M., Maldonado, V. et al. Pancreatic ductal adenocarcinomas from Mexican patients present a distinct genomic mutational pattern. Mol Biol Rep 47, 5175–5184 (2020). https://doi.org/10.1007/s11033-020-05592-3

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