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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Molecular and Cellular Oncology

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1658528

This article is part of the Research TopicNational Cancer Research Month 2025: Advances in Detection, Treatment and Therapies in OncologyView all 16 articles

The Mutational Landscape and Actionable Targets of Gallbladder Cancer: An Ancestry-Informed and Comparative Analysis of a Chilean Population

Provisionally accepted
José Ignacio EricesJosé Ignacio Erices1Evelin GonzálezEvelin González2Marcela SalgadoMarcela Salgado1Carol Barahona PonceCarol Barahona Ponce3Matías FreireMatías Freire4Gonzalo Sepúlveda-HermosillaGonzalo Sepúlveda-Hermosilla5Diego AmpueroDiego Ampuero4Alejandro BlancoAlejandro Blanco2Valentina Gárate-CalderónValentina Gárate-Calderón3Pablo BáezPablo Báez1Camilo Tapia-ValladaresCamilo Tapia-Valladares1Jessica ToroJessica Toro1Iván GallegosIván Gallegos1Olga BarajasOlga Barajas1Mónica AhumadaMónica Ahumada1Verónica SanhuezaVerónica Sanhueza6Loreto SpencerLoreto Spencer7Gonzalo De ToroGonzalo De Toro8Erik MoralesErik Morales9Lorena GutiérrezLorena Gutiérrez10Fernanda MoralesFernanda Morales1Arnaldo MarinArnaldo Marin1Nelson VarelaNelson Varela1Justo Lorenzo BermejoJusto Lorenzo Bermejo3Ricardo Armisen YañezRicardo Armisen Yañez2Katherine MarcelainKatherine Marcelain1*
  • 1Universidad de Chile, Santiago, Chile
  • 2Universidad del Desarrollo, Santiago, Chile
  • 3Universitat Heidelberg, Heidelberg, Germany
  • 4CORFO Center of Excellence in Precision Medicine, Pfizer Chile,, Santiago, Chile
  • 5CORFO Center of Excellence in Precision Medicine, Pfizer Chile, Santiago, Chile
  • 6Hospital Padre Hurtado, Santiago, Chile
  • 7Hospital Clínico Regional Guillermo Grant Benavente, Concepción, Chile
  • 8Universidad Austral de Chile, Valdivia, Chile
  • 9Hospital Regional de Talca, Talca, Chile
  • 10Hospital San Juan de Dios, Santiago, Chile

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Gallbladder cancer (GBC) is an aggressive malignancy with significant geographical variability; Chile reports one of the world's highest incidence rates. The absence of specific treatments necessitates new therapeutic strategies. However, the molecular characterization of GBC is scarce, particularly in high-risk Latin American populations, and the prevalence of predictive biomarkers appears to differ significantly across global studies, complicating the application of targeted therapies. To bridge this knowledge gap, this study aimed to define the genomic profile of GBC in a Chilean cohort using next-generation sequencing (NGS) to identify actionable variants and explore their association with genetic ancestry. We successfully sequenced 56 of 118 collected samples using a targeted gene panel. We identified 535 somatic mutations, with TP53 being the most frequently mutated gene (30%), followed by TSC2 (29%), NOTCH1 (27%), and KRAS (16%). Critically, 121 clinically actionable variants were found in key genes such as ATM, BRCA1/2, EGFR, and ERBB2, suggesting potential for targeted therapies already approved for other cancers. Our exploratory analysis also revealed a potential association between a higher proportion of Amerindian Ancestry and TP53 mutations. A comparative analysis with GBC cohorts from Japan, Singapore, and the USA confirmed that the Chilean cohort possesses distinct mutational patterns, reinforcing the need for population-specific research. Our findings provide a foundational genomic map for Chilean GBC, revealing actionable alterations that can support the development of personalized therapeutic strategies for this underserved patient population.

Keywords: gallbladder cancer, next-generation sequencing (NGS), driver mutations, genetic ancestry, Personalized therapies

Received: 02 Jul 2025; Accepted: 08 Sep 2025.

Copyright: © 2025 Erices, González, Salgado, Ponce, Freire, Sepúlveda-Hermosilla, Ampuero, Blanco, Gárate-Calderón, Báez, Tapia-Valladares, Toro, Gallegos, Barajas, Ahumada, Sanhueza, Spencer, De Toro, Morales, Gutiérrez, Morales, Marin, Varela, Lorenzo Bermejo, Armisen Yañez and Marcelain. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Katherine Marcelain, Universidad de Chile, Santiago, Chile

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material