Distinct Driver Pathway Enrichments and a High Prevalence of TSC2 Mutations in Right Colon Cancer in Chile: A Preliminary Comparative Analysis
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2024
Author(s)
Camilo Tapia-Valladares
Guillermo Valenzuela
Evelin González Feliú
Ignacio Maureira
Jessica Toro
Matías Freire
Gonzalo Sepúlveda-Hermosilla
Diego Ampuero
Alejandro Blanco
Iván Gallegos
Fernanda Morales
José I. Erices
Olga Barajas
Mónica Ahumada
Héctor R. Contreras
Jaime González
Katherine Marcelain
Type
journal-article
Abstract
<jats:p>Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of 40 Chilean CRC patients (Chp) using next-generation sequencing and compared them to data from mainly Caucasian cohorts (TCGA and MSK-IMPACT). We identified 388 mutations in 96 out of 135 genes, with TP53 (45%), KRAS (30%), PIK3CA (22.5%), ATM (20%), and POLE (20%) being the most frequently mutated. TSC2 mutations were associated with right colon cancer (44.44% in RCRC vs. 6.45% in LCRC, p-value = 0.016), and overall frequency was higher compared to TCGA (p-value = 1.847 × 10−5) and MSK-IMPACT cohorts (p-value = 3.062 × 10−2). Limited sample size restricts definitive conclusions, but our data suggest potential differences in driver mutations for Chilean patients, being that the RTK-RAS oncogenic pathway is less affected and the PI3K pathway is more altered in Chp compared to TCGA (45% vs. 25.56%, respectively). The prevalence of actionable pathways and driver mutations can guide therapeutic choices, but can also impact treatment effectiveness. Thus, these findings warrant further investigation in larger Chilean cohorts to confirm these initial observations. Understanding population-specific driver mutations can guide the development of precision medicine programs for CRC patients.</jats:p>
Cite this document
Tapia-Valladares, C., Valenzuela, G., González, E., Maureira, I., Toro, J., Freire, M., Sepúlveda-Hermosilla, G., Ampuero, D., Blanco, A., Gallegos, I., Morales, F., Erices, J. I., Barajas, O., Ahumada, M., Contreras, H. R., González, J., Armisén, R., & Marcelain, K. (2024). Distinct driver pathway enrichments and a high prevalence of tsc2 mutations in right colon cancer in chile: A preliminary comparative analysis. International Journal of Molecular Sciences, 25(9), 4695. https://doi.org/10.3390/ijms25094695
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