NEW YORK (GenomeWeb) – New research has revealed the extent to which cell lines evolve with time, leading to genetic and gene expression shifts that can change the way these lines respond to anti-cancer compounds and other drugs.
“[C]ancer cell lines remain a powerful tool for cancer research, but their genomic evolution leads to a high degree of variation across cell line strains, which must be considered in experimental design and data interpretation,” co-corresponding authors Todd Golub and Rameen Beroukhim of the Broad Institute, Dana-Farber Cancer Institute, and Harvard Medical School, and their colleagues wrote.
As they reported online today in Nature, the researchers considered exome sequence data for 106 human cell lines grown in parallel in labs in the US and UK. From there, they focused in on 27 versions of the same estrogen receptor-positive breast cancer cell line for more extensive genomic profiling, seeing signs of genetic diversification that were echoed in more than a dozen more cell lines.
Such genetic diversification was linked to gene expression shifts, anti-cancer drug responses, and other changes, while the team’s barcoding and single-cell analyses pointed to clonal selection and genomic instability that leads to heterozygosity within a line of cells that