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Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability

ABSTRACT: Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability

PROVIDER: PRJNA869575 | ENA |

REPOSITORIES: ENA

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Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability [methylation array]

Project description:Approximately 15% of colorectal cancer (CRC) patients present with high levels of microsatellite instability (MSI-H), which is driven by defective mismatch repair (dMMR). While about 20% of MSI-H tumors are associated with the hereditary condition, Lynch syndrome (LS), the majority develop through non-hereditary mechanisms. In recent years, the molecular processes underpinning tumor development in LS patients has been debated, with the longstanding view that dMMR is a secondary process in CRC development of LS patients being questioned. Here, we performed the first multi-omic analysis of normal colon organoids developed from LS and healthy patients to address questions regarding the development of dMMR in LS colon epithelial cells from cancer-free individuals.

2023-06-01 | GSE210018 | GEO

Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability [RNA-sequencing]

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Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability [methylation array]

Project description:Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability [methylation array]

| PRJNA863321 | ENA

Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability [RNA-sequencing]

Project description:Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability [RNA-sequencing]

| PRJNA869580 | ENA

Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-06-01 | GSE211222 | GEO

Colorectal cancers with microsatellite instability display unique miRNA profiles

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.

2011-11-22 | E-GEOD-30454 | biostudies-arrayexpress

Molecular subtype classification of urothelial carcinoma in Lynch syndrome

Project description:We aimed to provide a molecular description of Lynch syndrome-associated urothelial cancer in relation to molecular subtypes of sporadic bladder cancer. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with data from sporadic bladder cancer.

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Expression of immune-related genes in the normal colorectal mucosa and colorectal carcinoma samples from Lynch syndrome individuals

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.

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Msh2-Lynch

Project description:Msh2-Lynch

| PRJEB45308 | ENA

Colorectal cancers with microsatellite instability display unique miRNA profiles

2011-11-22 | GSE30454 | GEO