151. Somatic mutation landscape reveals differential variability of cell-of-origin for primary liver cancer
- Author
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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, and Hwajin Lee
- Subjects
Systems biology ,Biocomputational method ,Gene mutation ,Genomics ,Cancer research ,Bioinformatics-based prediction of cell-of-origin ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
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.
- Published
- 2020
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