Colorectal cancer cell lines lack the molecular heterogeneity of clinical colorectal tumors.
BACKGROUND
Histologically similar colorectal cancers (CRCs) exhibit a wide range of outcomes, suggesting that knowledge of the molecular differences might provide insight into this heterogeneity. Cancer cell lines have been used in preclinical studies to identify gene expression alterations that influence response to chemotherapeutic agents. However, it is not clear to what extent available CRC cell lines reflect the molecular heterogeneity observed in clinical colorectal tumors.


METHODS
We compared genome-wide gene expression data from 22 CRC cell lines and 276 clinical colorectal tumors to determine whether the cell lines were able to represent the variability in expression profiles seen in the clinical tissues. Following mean centered data normalization, hierarchical clustering was performed on the samples using literature-derived biologic and pharmacogenomic gene sets.


RESULTS
In general, the majority of cell lines tended to cluster together in a single group, as a subcluster within the clinical tissues, although a few cell lines showed distinct expression profiles from the majority of cell lines.


CONCLUSIONS
The gene expression data comparison suggests that CRC cell lines do not adequately reflect the molecular heterogeneity of clinical colorectal tumors.
Auman
James Todd
JT
UNC Institute of Pharmacogenomics and Individualized Therapy, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, 27599, USA. jtauman@e-mail.unc.edu
McLeod
Howard L
HL
D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor / Q000502:physiology*; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis
D014408:Biomarkers, Tumor