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

Heliyon

Yujin Hoshida¹  Rosa Karlić²  Hwajin Lee³  Sungmin Yang³  Kyungsik Ha³  Ning Zhang⁴  Fan Bai⁴  Ruidong Xue⁴  Chong Zhang⁴  Hidewaki Nakagawa⁵  Hong-Gee Kim⁶  Masashi Fujita⁶  Paz Polak⁷ 

[1] Laboratory of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China;Bioinformatics Group, Department of Molecular Biology, Division of Biology, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000, Zagreb, Croatia;Biomedical Knowledge Engineering Laboratory, Seoul National University, Seoul, 08826, South Korea;Biomedical Pioneering Innovation Center (BIOPIC) and Translational Cancer Research Center, School of Life Sciences, First Hospital, Peking University, Beijing, 100871, China;Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave., NY, 10029, USA;Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan;Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA;

关键词: Systems biology;    Biocomputational method;    Gene mutation;    Genomics;    Cancer research;    Bioinformatics-based prediction of cell-of-origin;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown