Project description:These samples have been analyzed for global alternative splicing variation on exon-level expression data using the FIRMA algorithm. We have identified and described transcriptome instability as a genome-wide, pre-mRNA splicing related characteristic of solid cancers. This Series consists of 19 normal colonic mucosa samples from colorectal cancer patients, and is an amendment to a larger series of colorectal cancer and adjacent normal colonic mucosa samples analyzed for gene expression at the exon-level (GSE24550).
Project description:Colorectal carcinomas arising in the context of Lynch syndrome, the most common inherited cancer syndrome, typically show deficiency of the DNA MMR (mismatch repair) system. Lack of functional MMR leads to accumulation of frameshift mutations at micosatellites (microsatellite instability, MSI). High load of highly immunogenic tumor-specific frameshift neoantigens results in strong immune response against Lynch syndrome MSI cancers. Previous studies have shown systemic immune responses against frameshift neoantigens in Lynch syndrome carriers long before tumor manifestation. In the present study, we analyzed the immune profile of normal colorectal mucosa in Lynch syndrome carriers without current or previous cancer history and in Lynch syndrome colorectal cancer patients, as well as of Lynch syndrome colorectal carcinomas. The unsupervised cluster analysis of gene expression data revealed a sharp differentiation between normal mucosa from Lynch syndrome individuals with and without manifest cancer as well as between normal mucosa in general and Lynch syndrome cancer tissue. Deconvolution analysis for predicting the prevalence of immune cell population among the three groups revealed 10 out of 14 investigated populations to be significantly different between the three tissue types (FDR=10%). In contrast to normal mucosa samples, tumor tissue showed overrepresentation of immune-suppressive cell populations, such as regulatory T cells and neutrophils. Taken together with the quantitative T cell density analysis on the basis of immunohistochemical T cell stainings, our data show strong immune infiltration of the normal colorectal mucosa in Lynch syndrome individuals even in the absence of a manifest cancer.
Project description:Colorectal cancer (CRC) is the third most common cancer worldwide. Colorectal polyps are recognised pre-cursors of CRC, however hyperplastic polyps lack malignant potential. The purpose of this study was to identify differences in gene expression between normal colonic mucosa, hyperplastic and adenomatous polyps from disease-free individuals. By comparing polyps believed to have malignant potential (adenomatous polyps) with hyperplastic polyps it is hoped that new insights into colorectal carcinogenesis can be achieved. 24 colonic samples comprising 8 normal colonic mucosa, 8 hyperplastic polyps and 8 adenomatous polyps.
Project description:Microsatellite instability (MSI), caused by defective mismatch repair, is observed in a subset of colorectal cancers (CRCs). We evaluated somatic mutations in microsatellite repeats of genes chosen based on reduced expression in MSI CRC and existence of a coding mononucleotide repeat. Expression profiling of 34 MSI colorectal cancers and 15 normal colonic mucosas was performed in 2002. Comparison of malignant and healthy tissue.
Project description:Analysis of microRNA expression of tumoral and non-tumoral colonic tissues. The aim of this study was to analyze the global miRNA signatures in various groups of well-characterized CRCs based on the presence of microsatellite instability (MSI). Total RNA from formalin-fixed paraffin-embedded tissue blocks from 4 different groups (normal colonic mucosa, Lynch syndrome tumors, sporadic MSI tumors and MSS tumors) was isolated using the RecoverAll Total Nucleic Acid Isolation Kit (Ambion) according to manufacturer instructions. MiRNA expression profiles were analyzed using miRNA microarray platform.
Project description:Colorectal cancer, one of the most frequent types of malignancy in the Western world, develops through a multi-step process. The main pathways establishing transformation of normal mucosa to invasive carcinoma include chromosomal instability (CIN), microsatellite instability (MSI) or epigenetic silencing through the CpG Island Methylator Phenotype (CIMP). These pathways have distinct clinical, pathological and genetic characteristics. In general, altered cell surface glycosylation has been linked to colorectal cancer progression, however the impact of MSI-specific pathways on the glycosylation machinery of MSI colon cancer cells has not been investigated yet. In a recent study (Patsos et al., 2009) we have shown that MSI-specific mutations induce marked alterations in cell surface glycosylation, indicating specific changes in the expression of glyco-genes. Therefore the purpose of our experiment is to define these changes by glyco-gene chip analysis.
Project description:Purpose: Examine H3K27ac enhancer and super-enhancer landscape differences between primary colorectal carcinoma and adjacent normal mucosa towards the identification of novel downstream targets. Methods: H3K27ac ChIP-seq and RNA-seq were performed on fresh primary colorectal carcinoma samples and normal colonic mucosa, from human patient samples. Results: We identified 2026 total super-enhancers in our cohort, between primary colorectal and normal mucosa. We quantified differences in H3K27ac signal within this space, between tumor and normal, and identified putative downstream target genes through integration with sample matched RNA-seq using a positive linear correlation model to identifty putative target genes.