Hepatocellular carcinoma cell lines retain the genomic and transcriptomic landscapes of primary human cancers

Citations Over TimeTop 11% of 2016 papers

Abstract

Hepatocellular carcinoma (HCC) cell lines are useful in vitro models for the study of primary HCCs. Because cell lines acquire additional mutations in culture, it is important to understand to what extent HCC cell lines retain the genetic landscapes of primary HCCs. Most HCC cell lines were established during the last century, precluding comparison between cell lines and primary cancers. In this study, 9 Chinese HCC cell lines with matched patient-derived cells at low passages (PDCs) were established in the defined culture condition. Whole genome analyses of 4 HCC cell lines showed that genomic mutation landscapes, including mutations, copy number alterations (CNAs) and HBV integrations, were highly stable during cell line establishment. Importantly, genetic alterations in cancer drivers and druggable genes were reserved in cell lines. HCC cell lines also retained gene expression patterns of primary HCCs during in vitro culture. Finally, sequential analysis of HCC cell lines and PDCs at different passages revealed their comparable and stable genomic and transcriptomic levels if maintained within proper passages. These results show that HCC cell lines largely retain the genomic and transcriptomic landscapes of primary HCCs, thus laying the rationale for testing HCC cell lines as preclinical models in precision medicine.

Related Papers

• → Application of comparative functional genomics to identify best-fit mouse models to study human cancer(2004)477 cited
• → Structure-based assessment and druggability classification of protein–protein interaction sites(2022)41 cited
• → Network motifs modulate druggability of cellular targets(2016)13 cited
• → Druggability Prediction(2012)5 cited
• Expression of PCAN and RAR-α in hepatocellular carcinoma(2002)