Genome and Transcriptome Profiles of CD133Positive Colorectal Cancer Cells

Section of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
American Journal Of Pathology (Impact Factor: 4.59). 04/2011; 178(4):1478-1488. DOI: 10.1016/j.ajpath.2010.12.036


Colorectal carcinomas (CRC) might be organized hierarchically and contain a subpopulation of tumorigenic, putative cancer stem cells that are CD133 positive. We studied the biological and genetic characteristics of such cells in CRC cell lines and primary tumors. Three CRC cell lines were sorted in CD133 positive and negative fractions. The respective genetic aberration profiles were studied using array comparative genomic hybridization (aCGH) and expression profiling. Tumorigenicity for each cellular population was tested by injection into nude mice. Additionally, we compared CD133+ and CD133- cells of 12 primary colorectal tumors using laser capture microdissection and aCGH. Three of five CRC cell lines displayed both CD133+ and CD133- cells, but tumorigenicity of these subfractions did not differ significantly and aCGH revealed essentially identical genomic imbalances. However, 96 genes were differentially expressed between the two populations. Array comparative genomic hybridization analysis after laser capture microdissection of CD133+ and CD133- areas in primary colorectal tumors revealed genetic differences in 7 of 12 cases. The use of cell lines for studying genomic alterations that define cancer stem cell characteristics, therefore, seems questionable. In contrast, CD133+ cells in primary cancer samples showed a unique genomic aberration profile. In conclusion, our data suggest that CD133 positivity defines a genetically distinct cellular compartment in primary CRC, which potentially includes tumor initiating cells.

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Available from: Maria R. Gaiser, Apr 29, 2014
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    • "The transcriptomes of colorectal cancers have been intensively investigated with high-throughput, array-based tools, which furnish quantitative, genome-wide descriptions of the individual gene expression levels associated with different cell phenotypes (e.g., adenoma cells vs. normal epithelial cells) [9-12]. More recently, other methods of analyzing gene expression data have been developed to gain additional insight into the mechanisms driving the phenotypic differences. "
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    • "The ANCA indices of the adenoma and carcinoma parts from malignant polyps differed significantly (ANCA index of the adenoma components 2.5; ANCA index of the carcinoma components 7.5; p=0.001), supporting evidence that chromosomal imbalances accumulate during CRC progression. The reported ANCA values are similar to those of previous studies (Ried et al., 1999; Habermann et al., 2007; Gaiser et al., 2011). "
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