El académico Andrés F. Cardona nos envía su investigación reciente:

Les comparto uno de los trabajos más excitantes que hemos hecho, esta vez en conjunto con el Broad Institute en Harvard. Después de muchos años de trabajo, hemos logrado encontrar el vinculo ancestral del cáncer de pulmón en LATAM con los asiáticos.

Title: Genetic ancestry contributes to somatic mutations in lung cancers from 2 admixed Latin American populations. Authors, Jian Carrot-Zhang y cols, Andres F. Cardona Foundation for Clinical and Applied Cancer Research – FICMAC, Bogotá, Colombia is a coauthor.

Inherited lung cancer risk, particularly in non-smokers, is poorly understood. Genomic and ancestry analysis of 1,153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden (TMB), and specific driver mutations in EGFR, KRAS, and STK11. A local Native American ancestry risk score predicted EGFR and KRAS mutation frequency more strongly than global ancestry, suggesting that germline genetics (rather than environmental exposure) underlie these disparities.

Significance:
The frequency of somatic EGFR and KRAS mutations in lung cancer varies by ethnicity but we do not understand why. Our study suggests that the variation in EGFR and KRAS is directly associated with genetic ancestry and suggests further studies to identify germline alleles that underpin this association.

Lung cancer that is typically driven by genomic alterations of genes in the receptor tyrosine kinase (RTK)/RAS/RAF pathway3 47 often allowing effective therapeutic targeting by RTK and other pathway inhibitors. It is well-known, but mysterious, that the frequency of somatic EGFR mutations is higher in LUADs from patients in East Asia (~45%) compared to LUADs from patients in Europe or patients of European (EUR) and/or African (AFR) descent in North America (~10%)4–8 51 . In Latin American countries, the frequency of somatic EGFR mutations in LUAD ranges from roughly 14% in Argentina, to 25-34% in Colombia, Brazil and Mexico, to 51% in Peru. Moreover, recent genomic studies from East Asian (EAS) and African (AFR) populations have suggested different distributions of tumor mutation burden (TMB) and levels of somatic copy number alteration (SCNA)12,13 56 , compared to LUAD patients of European (EUR) ancestry.

Despite the differences in patterns of somatic mutation between LUAD from patients of different ethnicity, the landscape of ancestry effects on the lung cancer genomes for the Latin American populations has not been comprehensively described; and it remains unknown whether the differences are due to ancestry-specific germline variation, or rather to population-specific environmental exposures (Fig. 1B). This is of particular importance as Native American (NAT) ancestry — which includes components of East Asian (EAS)

medRxiv preprint doi: https://doi.org/10.1101/2020.09.01.20183913.this version posted September 2, 2020.

Comentarios de académicos

¡Gran trabajo! Modelo de medicina traslacional. Llena uno de los principales vacíos de los estudios genéticos en enfermedades complejas (en este caso carcinoma de pulmón). Pocos estudios, como este, han evaluado la ancestría en cancer en América Latina y este el primero en sugerir efectos germinales sobre eventos somáticos.

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Internista-Endocrinólogo. Miembro de Número de la Academia Nacional de Medicina, Fellow del American College of Physicians y Miembro Honorario de la Asociación Colombiana de Endocrinología, Diabetes y Metabolismo. Editor Emérito de la Revista MEDICINA. Editor de Noticias, portal de la Academia www.anmdecolombia.org.co