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Whole genome sequencing of a Grem1 mutant human tumour

ABSTRACT: The BMP antagonist Grem1 has been shown to be associated with a rare human polyposis syndrome (HMPS). We have shown that there is a 40KB duplication on chrom 15 found in some patients with HMPS. Traditional serrated adenomas (rare sporadic polyps) share some morphological features with HMPS polyps and it has long been hypothesised that they are the sporadic version of HMPS polyps. We have obtained of one of these lesions and in this project we aim to characterise this tumour.

PROVIDER: EGAS00001000562 | EGA |

REPOSITORIES: EGA

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EGAS00001000562-sc-20160608 - samples

Project description:The BMP antagonist Grem1 has been shown to be associated with a rare human polyposis syndrome (HMPS). We have shown that there is a 40KB duplication on chrom 15 found in some patients with HMPS. Traditional serrated adenomas (rare sporadic polyps) share some morphological features with HMPS polyps and it has long been hypothesised that they are the sporadic version of HMPS polyps. We have obtained of one of these lesions and in this project we aim to characterise this tumour.

| EGAD00001002182 | EGA

Immune profiling of premalignant lesions in patients with Peutz-Jeghers Syndrome

Project description:RNA sequencing was performed in a total of 26 colorectal tissues from 26 unrelated patients including PJS polyps (n=6), familial adenomatous polyposis (FAP) polyps (n=9), paracancerous colonic mucosae (ConA) (n=9) as well as non-PJS and non-FAP sporadic polyps (ConB) (n=5)

2024-12-23 | GSE196711 | GEO

Gene expression data of organoids derived from traditional serrated adenomas

Project description:Traditional serrated adenomas (TSAs) are rare colorectal polyps characterized by unique histology features. Fusions in R-spondin genes have been found in TSAs, but it is not clear whether these are sufficient for TSA development. We established 2 patient-derived TSA organoid lines, and engineered chromosome rearrangements that involve R-spondin genes into human colonic organoids using CRISPR-Cas9. Consequently, we highlighted the similarity of the gene expression patterns between TSA organoids and engineered organoids.

2019-10-23 | GSE137336 | GEO

Specific serum methylome of the serrated pathway of colorectal carcinogenesis

Project description:This study was conducted to explore the serum methylome of precancerous lesions belonging to the serrated pathway of colorectal carcinogenesis in a prospective multicentre cohort. Individuals were grouped into five main categories: (i) serrated adenocarcinoma (SAC), (ii) high-risk serrated polyps (HR-SP) comprising traditional serrated adenomas (TSA), sessile serrated lesions (SSL), and serrated polyps (SP) with dysplasia or ≥ 10 mm; (iii) high-risk hyperplastic polyps (HR-HP), defined as HP ≥ 10 mm; (iv) low-risk serrated lesions (LR-SL) including SP without dysplasia < 10 mm and HP < 10 mm; and (v) healthy individuals with no colorectal findings (NCF). First, epigenome-wide methylation levels were quantified in pooled cfDNA samples to characterize the differential methylation profile between no serrated neoplasia (NSN: NCF and LR-SL) and high-risk serrated lesions (HR-SL: HR-HP and HR-SP); concordance with tissue methylation levels was assessed using external datasets. Then, the pathway-specific cfDNA methylation signature was evaluated together with cfDNA pools from the conventional CRC pathway. cfDNA was extracted from serum samples and methylation measurements were assessed with the Infinium MethylationEPIC BeadChip. Data was mainly preprocessed and analyzed with R/Bioconductor packages.

2024-03-01 | GSE199173 | GEO

Expression data from hyperplastic polyps and normal colonic mucosa from patients with familial and sporadic HPPS

2010-12-01 | GSE19963 | GEO

Transcriptomic profiles of advanced colorectal adenomas from 40 Korean patients

Project description:We report the RNA-seq data of 40 advanced colorectal adenoma patients form Dongguk University Ilsan International Hospital. The polyps with a diameter of 1cm or greater were regarded as advenced colorectal adenoma and obtained through colonoscopy. The data consist of 22 tublar adenoma, 6 tublovillous adenoma, 5 sessile serrated adenoma/polyp, 1 traditional serrated adenoma, intramucosal adenocarcinoma, neuroendocrine tumor, hyperplastic polyp, inflammatory polyp, high grade dysplasia, and atypical glands with adjacent hyperplastic mucosa.

2023-08-07 | GSE154548 | GEO

Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice [RNA-Seq]

Project description:The preferential localization of some neoplasms, such as serrated polyps, in specific areas of the intestine suggests that non-genetic factors may be important for their development. To test this hypothesis, we took advantage of transgenic mice that expressed HB-EGF throughout the intestine, but develop serrated polyps only in the cecum. Here we show that a host-specific microbiome was associated with serrated polyps, and that alterations of the microbiota induced by antibiotic treatment or by embryo-transfer rederivation markedly inhibited the formation of serrated polyps in the cecum. Mechanistically, development of serrated polyps was associated with a local decrease in epithelial barrier-function, bacterial invasion, production of antimicrobials, and increased expression of several inflammatory factors such as IL-17, Cxcl2, Tnf-α, and IL-1. Increased number of neutrophils were found within the serrated polyps, and their depletion significantly reduced polyp growth. Together these results indicate that non-genetic factors contribute to the development of serrated polyps and suggest that the development of these intestinal neoplasms in the cecum is driven by the interplay between genetic changes in the host, an inflammatory response, and a host-specific microbiota.

2014-02-12 | GSE47735 | GEO

Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice [BeadArray]

2014-02-12 | GSE47734 | GEO

Expression data from hyperplastic polyps and normal colonic mucosa from patients with familial and sporadic HPPS

Project description:Expression data from hyperplastic polyps and normal colonic mucosa from patients with familial and sporadic hyperplastic polyposis syndrome (HPPS). We aim to characterize at a molecular level a cohort of hyperplastic lesions from HPPS patients with and without family history. RNA from hyperplastic polyps and normal colonic mucosa (proximal and distal) from patients with familial and sporadic HPPS were included in this study. Total RNA was isolated from each tissue sample, quantified and its quality evaluated. cRNA preparation, hybridization and analysis of results was performed according to Affymetrix recommendations. cRNA was hybridised in the GeneChip array (Human Genome U133 Plus 2.0, Affymetrix), and the intensity was measured.

2010-12-01 | E-GEOD-19963 | biostudies-arrayexpress

MicroRNA signatures of colonic adenomas according to histology

Project description:Adenomatous polyps adjacent to colorectal cancer (CRC) were found to exhibit two distinct microRNAs (miRs) patterns from normal mucosa to low- and separately, to high-grade dysplasia; presence in screen-detected adenoma of non-cancer patients is unknown. Global miR expression was performed on biopsies obtained from 109 healthy patients undergoing screening/surveillance colonoscopy. Included were normal mucosa (NM); hyperplastic polyp (HP); tubular adenoma (TA), tubulovillous adenoma, with or without, high-grade dysplasia (TVHG) and serrated-polyps; sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA). Logistic regression was used to model miRs predictive of histology and CRC risk. We identified 99 miRs that differed across five histologic groups (FDR=0.05) and that accurately separated on histology (Concordance Index (CI)=0.96). In HPNM, miRs-145, -143, -107a, -23b, and -24 were upregulated whereas miRs-663, -1268, -320b, -1275, and -671 where overexpressed in TVHGs (FDR P<0 .05). The expression of miR-145 and -30a showed high accuracy to separate low from high-risk polyps independent of serrated status (CI= 97.1%; AUC 93.4%). For TSAs, miR-125b and -199a were uniquely downregulated relative to HPNMs and miR-335 discriminated between non-serrated and serrated histology. Histologically advanced polyps from non-cancer patients share miR alterations with those reported for CRC and high-grade adenoma adjacent to tumor including downregulation of immune regulatory miRs-125 and -199a in TSAs; polyp that frequently present with in situ carcinoma. These data extend evidence that miR patterns of high-risk adenoma are detectable in subset of screen-detected adenoma for which measurement may be useful in in adenoma risk stratification.

2015-09-29 | GSE73487 | GEO

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