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

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

Izvornik
Heliyon (2405-8440) 6 (2020), 2; 1-9

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Biocomputational method ; Bioinformatics-based prediction of cell-of-origin ; Cancer research ; Gene mutation ; Genome and single-cell RNA-Seq data ; Genomics ; Integration of epigenome ; Primary liver cancers ; Systems biology

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA