Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Complex Patterns of Altered MicroRNA Expression during the Adenoma-Adenocarcinoma Sequence for Microsatellite-stable Colorectal Cancer

ABSTRACT: We searched the database of the Department of Pathology at The University of Texas MD Anderson Cancer Center and selected 21 patients who had invasive microsatellite-stable colorectal adenocarcinoma arising from a pre-existing adenoma and adjacent non-neoplastic mucosa in a resection specimen to permit pairwise analyses, and who had informed consent for research use of their residual tissue. A hematoxylin and eosin (H&E)-stained slide from each formalin-fixed paraffin-embedded tissue block was used to select one block that had invasive adenocarcinoma and adenoma with low- and high-grade dysplasia with minimal contamination by stromal and inflammatory cells, and adjacent full thickness non-neoplastic mucosa including the surface epithelium and proliferative zone. Unstained recut slides with 5-micrometer sections and no coverslip were laid over the marked slide, and the corresponding demarcated areas were manually microdissected.

ORGANISM(S): Homo sapiens

SUBMITTER: Angela Bartley

PROVIDER: E-MTAB-813 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Complex patterns of altered MicroRNA expression during the adenoma-adenocarcinoma sequence for microsatellite-stable colorectal cancer.

Bartley Angela N AN Yao Hui H Barkoh Bedia A BA Ivan Cristina C Mishra Bal M BM Rashid Asif A Calin George A GA Calin George A GA Luthra Rajyalakshmi R Hamilton Stanley R SR

Clinical cancer research : an official journal of the American Association for Cancer Research 20110923 23

<h4>Purpose</h4>MicroRNAs are short noncoding RNAs that regulate gene expression and are over- or underexpressed in most tumors, including colorectal adenocarcinoma. MicroRNAs are potential biomarkers and therapeutic targets and agents, but limited information on microRNAome alterations during progression in the well-known adenoma-adenocarcinoma sequence is available to guide their usage.<h4>Experimental design</h4>We profiled 866 human microRNAs by microarray analysis in 69 matched specimens of ...[more]

PMID: 21948089

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Project description:BACKGROUND & AIM: Sessile serrated adenoma/polyps (SSA/Ps) are the likely culprit of ~20% colon cancers but they are molecularly poorly understood. We investigated their epigenetic phenotype using high-throughput analysis of DNA methylation and gene expression. METHODS: 17 SSA/Ps and, as a comparative group, 15 conventional adenomas (all with matched samples of normal mucosa) were prospectively collected during colonoscopy. DNA from the 64 tissues was analyzed, via bisulfite next generation sequencing, for methylation at ~2.7 million CpG sites located prevalently in gene regulatory regions spanning 80.5Mb (~2.5% of the genome). The transcriptome of these samples was also investigated using RNA sequencing. An independent series of 61 archival lesions was used for targeted verification of DNA methylation. RESULTS: Both SSA/Ps and conventional adenomas showed a profound remodelling of their methylome. Cytosine hypermethylation was more pervasive in SSA/Ps than adenomas, in terms of number of hypermethylated regions (22,147 vs 15,965, respectively) and genes (4938 vs 3443, respectively). In addition, the extent of hypermethylation in a given region was higher in SSA/Ps than adenomas. This methylation pattern of SSA/Ps was reminiscent of the CpG island methylator phenotype (CIMP) of their descendant cancers. We have called this phenotype proto-CIMP since most of the hypermethylation occurred in CpG islands and shores. SSA/Ps were also protected from a wave of demethylation that instead occurred in adenomas outside of CpG islands/shores (4288 vs 18,417 hypomethylated regions in SSAPs vs adenomas). Verification studies of six hypermethylated regions demonstrated the high potential of DNA methylation markers for predicting the diagnosis of SSA/Ps and/or adenomas. Proto-CIMP of SSA/Ps was surprisingly associated with a higher number of up- (618) than downregulated (349) genes, while adenomas showed the opposite trend (516 up- vs 712 downregulated genes). CONCLUSIONS: The epigenetic landscape of SSA/Ps differs substantially from that of conventional adenomas. This huge amount of epigenetic variation represents a rich source of promising diagnostic tools, such as novel DNA markers or histologic stainings, for the tailored management of the two most frequent colon cancer precursors.

Dataset Information

Complex Patterns of Altered MicroRNA Expression during the Adenoma-Adenocarcinoma Sequence for Microsatellite-stable Colorectal Cancer

Publications

Complex patterns of altered MicroRNA expression during the adenoma-adenocarcinoma sequence for microsatellite-stable colorectal cancer.

Similar Datasets

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