Evaluating cell lines as tumour models by comparison of genomic profiles

TLDR

Cancer cell lines are widely used as in vitro tumour models, and recent large‑scale molecular profiling from the Cancer Cell Line Encyclopedia and the Cancer Genome Atlas enables systematic genomic comparisons between cell lines and tumours. The study aims to identify ovarian cancer cell lines with the highest genetic similarity to ovarian tumours. The authors analysed 47 ovarian cancer cell lines using genomic profiling to assess similarity to tumour samples. The analysis revealed marked differences between commonly used ovarian cancer cell lines and high‑grade serous ovarian cancer tumours, identified rarely used lines that more closely match tumour profiles, and suggested that genomically informed cell line selection can bridge the cell line–tumour gap for all tumour types.

Abstract

Cancer cell lines are frequently used as in vitro tumour models. Recent molecular profiles of hundreds of cell lines from The Cancer Cell Line Encyclopedia and thousands of tumour samples from the Cancer Genome Atlas now allow a systematic genomic comparison of cell lines and tumours. Here we analyse a panel of 47 ovarian cancer cell lines and identify those that have the highest genetic similarity to ovarian tumours. Our comparison of copy-number changes, mutations and mRNA expression profiles reveals pronounced differences in molecular profiles between commonly used ovarian cancer cell lines and high-grade serous ovarian cancer tumour samples. We identify several rarely used cell lines that more closely resemble cognate tumour profiles than commonly used cell lines, and we propose these lines as the most suitable models of ovarian cancer. Our results indicate that the gap between cell lines and tumours can be bridged by genomically informed choices of cell line models for all tumour types.