Heliyon (Feb 2020)

Somatic mutation landscape reveals differential variability of cell-of-origin for primary liver cancer

  • Kyungsik Ha,
  • Masashi Fujita,
  • Rosa Karlić,
  • Sungmin Yang,
  • Ruidong Xue,
  • Chong Zhang,
  • Fan Bai,
  • Ning Zhang,
  • Yujin Hoshida,
  • Paz Polak,
  • Hidewaki Nakagawa,
  • Hong-Gee Kim,
  • Hwajin Lee

Journal volume & issue
Vol. 6, no. 2
p. e03350

Abstract

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Primary liver tissue cancer types are renowned to display a consistent increase in global disease burden and mortality, thus needing more effective diagnostics and treatments. Yet, integrative research efforts to identify cell-of-origin for these cancers by utilizing human specimen data were poorly established. To this end, we analyzed previously published whole-genome sequencing data for 384 tumor and progenitor tissues along with 423 publicly available normal tissue epigenomic features and single cell RNA-seq data from human livers to assess correlation patterns and extended this information to conduct in-silico prediction of the cell-of-origin for primary liver cancer subtypes. Despite mixed histological features, the cell-of-origin for mixed hepatocellular carcinoma/intrahepatic cholangiocarcinoma subtype was predominantly predicted to be hepatocytic origin. Individual sample-level predictions also revealed hepatocytes as one of the major predicted cell-of-origin for intrahepatic cholangiocarcinoma, thus implying trans-differentiation process during cancer progression. Additional analyses on the whole genome sequencing data of hepatic progenitor cells suggest these cells may not be a direct cell-of-origin for liver cancers. These results provide novel insights on the nature and potential contributors of cell-of-origins for primary liver cancers.

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