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Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node–Negative and Lymph Node–Positive Colon Carcinomas

¹ Department of General Surgery, University Medical Center, Göttingen, Germany and ² Genetics Branch and ³ Biometrics Research Branch, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Thomas Ried, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Room 1408, Building 50, 50 South Drive, Bethesda, MD 20892-8010. Phone: 301-594-3118; Fax: 301-435-4428; E-mail: riedt{at}mail.nih.gov or B. Michael Ghadimi, Department of General Surgery, University Medical Center, Robert-Koch-Str. 40, 37075 Göttingen, Germany. Phone: 49-551-39-6162; Fax: 49-551-39-6106; E-mail: mghadim{at}uni-goettingen.de.

To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P < 1e–7). A significant proportion of these genes mapped to chromosome 20 (P = 0.01). Seventeen genes had a >5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node–negative and lymph node–positive tumors (P < 0.001), the functional annotation of which revealed a preponderance of genes that play a role in cellular immune response and surveillance. The microarray-derived gene expression levels of 20 deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/ß-catenin signaling cascade, suggesting similar pathogenic pathways. [Cancer Res 2007;67(1):41–56]

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				Correction: January 1, 2007 Cover Cancer Res., February 15, 2007; 67(4): 1877 - 1877. [Full Text] [PDF]