James Todd Auman1, Howard L McLeod. 1. 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
Abstract
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. MATERIALS AND 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. CONCLUSION: The gene expression data comparison suggests that CRC cell lines do not adequately reflect 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. MATERIALS AND 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. CONCLUSION: The gene expression data comparison suggests that CRC cell lines do not adequately reflect the molecular heterogeneity of clinical colorectal tumors.
Authors: Jaine K Blayney; Timothy Davison; Nuala McCabe; Steven Walker; Karen Keating; Thomas Delaney; Caroline Greenan; Alistair R Williams; W Glenn McCluggage; Amanda Capes-Davis; D Paul Harkin; Charlie Gourley; Richard D Kennedy Journal: Nucleic Acids Res Date: 2016-06-28 Impact factor: 16.971
Authors: Andreas Schlicker; Garry Beran; Christine M Chresta; Gael McWalter; Alison Pritchard; Susie Weston; Sarah Runswick; Sara Davenport; Kerry Heathcote; Denis Alferez Castro; George Orphanides; Tim French; Lodewyk F A Wessels Journal: BMC Med Genomics Date: 2012-12-31 Impact factor: 3.063