ArticleHepatology international2023
Molecular evolution in different subtypes of multifocal hepatocellular carcinoma.
Article in Hepatology international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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11 authors at 6 institutions in 2 countries.
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Abstract
backgroundMultifocal hepatocellular carcinoma (MF-HCC) accounts for > 40% of HCCs, exhibiting a poor prognosis than single primary HCCs. Characterizing molecular features including dynamic changes of mutational signature along with clonal evolution, intrahepatic metastatic timing, and genetic footprint in the preneoplastic stage underlying different subtypes of MF-HCC are important for understanding their molecular evolution and developing a precision management strategy.
methodsWe conducted whole-exome sequencing in 74 tumor samples from spatially distinct regions in 35 resected lesions and adjacent noncancerous tissues from 11 patients, 15 histologically confirmed preneoplastic lesions, and six samples from peripheral blood mononuclear cells. A previously published MF-HCC cohort (n = 9) was included as an independent validation dataset. We combined well-established approaches to investigate tumor heterogeneity, intrahepatic metastatic timing, and molecular footprints in different subtypes of MF-HCCs.
resultsWe classified MF-HCCs patients into three subtypes, including intrahepatic metastasis, multicentric occurrence, and mixed intrahepatic metastasis and multicentric occurrence. The dynamic changes in mutational signatures between tumor subclonal expansions demonstrated varied etiologies (e.g., aristolochic acid exposure) underlying the clonal progression in different MF-HCC subtypes. Furthermore, the clonal evolution in intrahepatic metastasis exhibited an early metastatic seeding at 10
conclusionOur study comprehensively characterized the varied tumor clonal evolutionary history underlying different subtypes of MF-HCC and provided important implications for optimizing personalized clinical management for MF-HCC.
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