Global gene expression analysis of development and progression of colorectal carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE77953 | GEO | 2016/05/13
SECONDARY ACCESSION(S): PRJNA312197
REPOSITORIES: GEO
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Project description:Colorectal cancer (CRC) tumorigenesis proceedes through well defined clinical stages assoicated with charateristic mutations. To get a better understanding of CRC progression at the transcriptional level, we performed transcriptome profiling on samples from normal colonic tissues, pre-malignant adenomas, carcinomas and metatases. We used Affymatrix microarry to get a broad view of gene expression during colorectal cancer progression and identified significantly differentially expressed genes between different stages A total of 58 laser capture micro-dissected tissues that cover the major stages of colorectal cancer progression were collected from the Department of Pathology at the University of Virginia under the supervision of an experienced pathologist. DNA was extracted and run on Affymetrix microarrys. Gene-expression profiles were collected on Affymetrix HG-U133A GeneChips according to the manufacturerâs instructions.
2016-05-13 | E-GEOD-77953 | biostudies-arrayexpress
Project description:Colorectal tumorigenesis proceedes through well defined clinical stages assoicated with charateristic mutations. Besides genetic alterations, epi-driver genes that are aberrantly expressed in cancers in a fashion that confers a seletive growth advantage can also contribute to tumor evolution. To gain a global view of methylation patterns in normal and maliganant colorectal epithelia, we performed genome-wide DNA methylation analysis on DNAs from 48 fresh frozen CRC samples at different stages of CRC progression. We used IlluminaHumanMethylation450 Beadchip to get a broad view of genome-wide DNA methylationdata during CRC progression and identified significantly differentially methylated genes during CRC progression A total of 48 macro-dissected tissues including normal colon tissue, adenomas, carcinomas and metastases were collected by the Department of Pathology at the University of Virginia under the supervision of an experienced pathologist. DNA was extracted and run on IlluminaHumanMethylation450 Beadchip by Expression Analyisis.
2016-05-13 | E-GEOD-77954 | biostudies-arrayexpress
Project description:Colorectal tumorigenesis proceedes through well defined clinical stages assoicated with charateristic mutations. Besides genetic alterations, epi-driver genes that are aberrantly expressed in cancers in a fashion that confers a seletive growth advantage can also contribute to tumor evolution. To gain a global view of methylation patterns in normal and maliganant colorectal epithelia, we performed genome-wide DNA methylation analysis on DNAs from 48 fresh frozen CRC samples at different stages of CRC progression. We used IlluminaHumanMethylation450 Beadchip to get a broad view of genome-wide DNA methylationdata during CRC progression and identified significantly differentially methylated genes during CRC progression
2016-05-13 | GSE77954 | GEO
Project description:Colorectal adenomas are precursor lesions of colorectal cancers and represent clonal amplifications of single cells from colonic crypts. DNA methylation patterns specify cell-type identity during cellular differentiation and therefore provide novel opportunities for the molecular analysis of tumors. We have now analyzed DNA methylation patterns in colorectal adenomas and identified three biologically defined subclasses that describe different intestinal crypt differentiation stages. Importantly, colorectal carcinomas could be classified into the same methylation subtypes, reflecting their shared cell-types of origin with adenomas. Further data analysis also revealed significantly reduced overall survival for one of the subtypes. Our results establish a novel concept for understanding the methylation patterns observed in colorectal cancer and provide opportunities for tumor subclassification and patient stratification.
2018-06-12 | E-MTAB-6450 | biostudies-arrayexpress
Project description:Chromosomal instability (CIN) is the hallmark of colorectal adenoma to carcinoma progression in 85% of cases, with 20q gain as the most prominent aberration. Yet, the oncogenes at this chromosomal gain are still largely unknown. Here, we aimed to identify oncogenes at 20q involved in colorectal adenoma to carcinoma progression by measuring the effect of 20q gain on gene expression in this amplicon. Segmentation of DNA copy number changes on 20q was performed by array CGH in 67 colorectal adenomas and carcinomas. Additionally, robust analysis of mRNA expression in these segments was performed in 68 adenomas and carcinomas. This approach revealed seven genes to be important in CIN related adenoma to carcinoma progression. These genes may both serve as highly specific biomarkers for presence of high-risk precursor lesions as well as potential targets for pharmaceutical intervention. Keywords: Integration of array CGH and expression microarrays in colorectal cancer progression We performed array CGH on a panel of 41 progressed adenomas, from which the adenoma and carcinoma components were separately analysed (total, 82 samples). The DNA obtained from these samples was extracted from formalin-fixed, paraffin-embedded material. Additionally we analysed a series of independent frozen adenomas and carcinomas by array CGH (34 adenomas and 33 carcinomas) and expression microarrays (37 adenomas and 31 carcinomas). For array-CGH we used as reference DNA for all samples, a pool of 10 normal individuals. For expression microarrays we used as reference a commercial available RNA (pool of different cancer cell lines), from Strategene. No replicates nor dye swaps were done.
2010-06-25 | E-GEOD-8067 | biostudies-arrayexpress
Project description:Background: Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathological, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. Results: To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues, but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent over- and underexpression of 78 known components of this signaling cascade. Conclusions: Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis. Keywords: tissue comparison
2007-08-03 | GSE8671 | GEO
Project description:Approximately two decades ago, Vogelstein and Fearon proposed the adenoma-carcinoma sequence of sporadic CRC development and illustrated the accumulation of genetic alterations during the stepwise progression, thereby providing a guideline for clinical practice. Although the detection and excision of precancerous lesions could prevent colorectal cancer and reduce mortality, 6% of adenomas will ultimately develop into colorectal cancer. Thus, this genetic model for colorectal tumorigenesis may not completely reflect the complex essence of the disease and whether the mode of initiation of the events in the multistep progression affects the outcome of CRC is still unknown. In this study, mRNA and miRNA expression profiling was performed with human colorectal tissues, including normal mucosa, adenoma and adenocarcinoma. Then, an integrated approach was adopted to establish the regulatory interaction networks that were correlated with colorectal carcinogenesis. Finally, a 55-gene signature whose expression was down-regulated in precancerous lesions compared to normal tissue was identified as a potential early indicator of CRC survival. The results suggested that genes related to immunity and homeostasis played a critical role in protection against adenoma initiation and that the altered molecular events that influence colorectal cancer prognosis may be set in an early, precancerous stage. Four types of human colorectal tissues were selected by colonoscopic resection or colorectal surgery, including 12 normal mucosae, 21 low-grade adenomas (mild or moderate atypical hyperplasia), 30 high-grade adenomas (severe atypical hyperplasia or carcinoma in situ) and 25 adenocarcinomas. Gene expression profiling analysis of these samples was performed using Agilent 4x44K human whole genome gene expression microarray (G4112F).
2015-10-16 | E-GEOD-41657 | biostudies-arrayexpress
Project description:Approximately two decades ago, Vogelstein and Fearon proposed the adenoma-carcinoma sequence of sporadic CRC development and illustrated the accumulation of genetic alterations during the stepwise progression, thereby providing a guideline for clinical practice. Although the detection and excision of precancerous lesions could prevent colorectal cancer and reduce mortality, 6% of adenomas will ultimately develop into colorectal cancer. Thus, this genetic model for colorectal tumorigenesis may not completely reflect the complex essence of the disease and whether the mode of initiation of the events in the multistep progression affects the outcome of CRC is still unknown. In this study, mRNA and miRNA expression profiling was performed with human colorectal tissues, including normal mucosa, adenoma and adenocarcinoma. Then, an integrated approach was adopted to establish the regulatory interaction networks that were correlated with colorectal carcinogenesis. Finally, a 55-gene signature whose expression was down-regulated in precancerous lesions compared to normal tissue was identified as a potential early indicator of CRC survival. The results suggested that genes related to immunity and homeostasis played a critical role in protection against adenoma initiation and that the altered molecular events that influence colorectal cancer prognosis may be set in an early, precancerous stage. Four types of human colorectal tissues were selected by colonoscopic resection or colorectal surgery, including 15 normal mucosae, 39 low-grade adenomas (mild or moderate atypical hyperplasia), 20 high-grade adenomas (severe atypical hyperplasia or carcinoma in situ) and 33 adenocarcinomas. MicroRNA expression profiling analysis of these samples was performed on Agilent 8Ã16K Human miRNA Microarray V3 (G4470C).
2015-10-16 | E-GEOD-41655 | biostudies-arrayexpress
Project description:Somatic L1 retrotransposition events have been shown to occur in epithelial cancers1-8. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), we studied different stages of four colorectal cancers arising from colonic polyps, seven pancreatic carcinomas, as well as seven gastric cancers. Surprisingly, we found somatic L1 insertions not only in all cancer types and metastases, but also in colonic adenomas, well-known cancer precursors. Some insertions were also present in low quantities in normal GI tissues, occasionally caught in the act of being clonally fixed in the adjacent tumors. Insertions in adenomas and cancers numbered in the hundreds and many were present in multiple tumor sections implying clonal distribution. Our results demonstrate that extensive somatic insertional mutagenesis occurs very early during the development of GI tumors, probably before dysplastic growth. Here we show Human SNP 6.0 Array experiments on DNAs from four colorectal cancer patients (1BV, 2BV, 3BV, and 4BV) with polyps and metastases. Here we characterize the samples for CNVs and compare the samples' CNV status to their respective somatic L1 retrotransposition profile.
2015-08-10 | E-GEOD-63601 | biostudies-arrayexpress
Project description:We performed the sampling of multiple single tumour glands from 8 colorectal carcinomas and 3 adenomas with the aim of inferring tumour evolutionary dynamics and reconstruct the timeline of progression
2014-12-22 | E-MTAB-2140 | biostudies-arrayexpress