ArticleEBioMedicine2026
Geographic and genetic diversity in gallbladder cancer mutation profiles: insights from a worldwide exome analysis.
Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundGallbladder cancer (GBC), an aggressive disease with limited treatment options, occurs mainly in low-income and middle-income regions of Asia and Latin America. We analysed whole-exome sequencing data from 262 GBC tumour-normal sample pairs from Chilean, Chinese, Indian, Japanese and South Korean patients to investigate differences in GBC mutation profiles according to geographic location and genetic ancestry.
methodsWe used a unified analysis pipeline to ascertain gene mutations and mutational signatures, estimated the individual proportions of major ancestry subtypes in the investigated cohorts, and examined the relationship between genetic and genomic profiles.
findingsThe tumour mutation burden (TMB) was highest in China and lowest in Chile (p < 0.0001 [F-test]). The most frequently mutated genes included TP53, MUC16, ELF3, and ARID2. The most common mutational signatures were single-base substitution (SBS)5, SBS1, and SBS13. We observed differences between cohorts in the frequency of specific gene mutations and mutational signatures, as well as associations between the major ancestry subtypes in the investigated cohorts and (1) TMB, (2) the frequencies of MACF1 and MUC16 mutations, and (3) the frequencies of SBS5, SBS13, and SBS29. For example, TMB increased by 0.08 (95%CI 0.03-0.14) for every 1% increase in the proportion of Japanese ancestry.
interpretationGBC exhibits marked geographic and genetic heterogeneity in its mutation profiles, which could have relevant implications for prevention and targeted therapy in the high-incidence regions investigated.
fundingThis study was supported by the European Union's Horizon 2020 research and innovation programme (grant 825741) and the German Academic Exchange Service (DAAD; grant 91762082).
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