Dataset Information

Colon_Illumina_2.5M_Cases - samples

ABSTRACT: Colon tumour samples

PROVIDER: EGAD00010000272 | EGA |

REPOSITORIES: EGA

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Publications

Recurrent R-spondin fusions in colon cancer.

Seshagiri Somasekar S Stawiski Eric W EW Durinck Steffen S Modrusan Zora Z Storm Elaine E EE Conboy Caitlin B CB Chaudhuri Subhra S Guan Yinghui Y Janakiraman Vasantharajan V Jaiswal Bijay S BS Guillory Joseph J Ha Connie C Dijkgraaf Gerrit J P GJ Stinson Jeremy J Gnad Florian F Huntley Melanie A MA Degenhardt Jeremiah D JD Haverty Peter M PM Bourgon Richard R Wang Weiru W Koeppen Hartmut H Gentleman Robert R Starr Timothy K TK Zhang Zemin Z Largaespada David A DA Wu Thomas D TD de Sauvage Frederic J FJ

Nature 20120801 7413

Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and r ...[more]

PMID: 22895193

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Project description:In response to polarization cues, cultured Caco-2 cells, a human colon adenocarcinoma-derived cell line, form a polarized epithelium resembling normal enterocytes. We investigated potential signaling mechanisms activated by Caco-2 cells that might trigger the genome-wide transcriptional reprogramming that accompanies polarization (Saaf et al, submitted-I). cDNA microarrays were used to compare the transcriptional profile of Caco-2 polarization to the gene expression profiles of normal human colon and colon tumors. The transcript profile of proliferating, non-polarized Caco-2 cells has striking parallels to the gene expression profile of human colon cancer in vivo. However, as Caco-2 cells develop polarity, the gene expression profile shifts to one more closely resembling that of normal colon tissue, suggesting that the underlying regulatory mechanisms that mediate Caco-2 cell polarization are similar to those that occur during in vivo enterocyte differentiation. We show that transcriptional re-programming of Caco-2 cells during development of cell polarity occurs in the context of signaling pathways that are regulated in a manner that is remarkably similar to those in normal intestinal development. For example, transcriptional targets of the Wnt pathway are tightly regulated during Caco-2 cell polarization, mimicking the gradient of Wnt-mediated transcription in the crypt (high expression) to villus (low expression) axis in human intestine. However, Caco-2 cells lack full-length APC necessary for normal Wnt-regulated degradation of beta-catenin. Biochemical analysis indicates that regulation of the Wnt pathway occurs in the nucleus at the level of activation of target genes by the beta-catenin-TCF complex, revealing a novel additional mechanism by which intestinal cells may regulate Wnt signaling during their maturation. In addition, other signaling pathways including Notch, BMP, Hedgehog, and growth factor, were temporally regulated during Caco-2 cell polarization. Surprisingly, modulation of these signaling pathways in Caco-2 cells occurs in the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. This dataset contains gene expression profiles of 9 normal colon samples and 15 colon tumor samples. Samples of tumor and normal colon mucosa were collected from colon cancer resection from Department of Surgery, Queen Mary Hospital University of Hong Kong. Tissue was frozen in liquid nitrogen within 30 min of resection. Nonneoplastic mucosa from colon was dissected free of muscle and histologically confirmed to be tumor free by frozen section. Total RNA was extracted using Trizol (Invitrogen, Carlsbad, CA) from each tissue sample and processed for microarray hybridization. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: Tumor/Normal colon samples Keywords: disease_state_design

Dataset Information

Colon_Illumina_2.5M_Cases - samples

Publications

Recurrent R-spondin fusions in colon cancer.

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