RNA sequencing of Esophageal adenocarcinomas
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE94869 | GEO | 2017/02/15
SECONDARY ACCESSION(S): PRJNA374673
REPOSITORIES: GEO
Similar Datasets
Project description:The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With an extremely poor five-year survival rate of only 15%, identification of new therapeutic targets for EAC is of great importance. Here, we analyze the mutation spectra from the whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a novel mutational signature in EACs defined by a high prevalence of A to C transversions at Ap*A dinucleotides. Statistical analysis of the exome data identified 26 genes that are mutated at a significant frequency. Of these 26 genes, only four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include several chromatin modifying factors and candidate contributors to EAC: SPG20, TLR4, ELMO1, and DOCK2. Notably, functional analyses of EAC-derived mutations in ELMO1 increase cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis. The study aimed to analyze 150 primary, human esophageal adenocarcinoma samples by whole genome and whole exome sequencing (which will be deposited to dbGAP following the TCGA practice). RNA expression data was used to determine gene expression in 14 of the samples analyzed by whole genome sequencing. No normals were analyzed.
2013-02-11 | E-GEOD-42363 | biostudies-arrayexpress
Project description:The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With an extremely poor five-year survival rate of only 15%, identification of new therapeutic targets for EAC is of great importance. Here, we analyze the mutation spectra from the whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a novel mutational signature in EACs defined by a high prevalence of A to C transversions at Ap*A dinucleotides. Statistical analysis of the exome data identified 26 genes that are mutated at a significant frequency. Of these 26 genes, only four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include several chromatin modifying factors and candidate contributors to EAC: SPG20, TLR4, ELMO1, and DOCK2. Notably, functional analyses of EAC-derived mutations in ELMO1 increase cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis.
2013-02-11 | GSE42363 | GEO
Project description:Background and aims: The aim of this study was to analyze the molecular characteristics of adenocarcinoma of the gastroesophageal junction (AGEJ) compared to esophageal (EAC) and gastric adenocarcinomas (GCFB) from The Cancer Genome Atlas (TCGA) and Seoul National University (SNU) cohorts using next-generation sequencing. Methods: Based on mRNA expression of EAC (n=78) and GCFB (n=102) from the TCGA cohort, a molecular classification model using the Bayesian compound covariate predictor classified AGEJ/cardia (n=48) from the TCGA cohort and AGEJ/upper third gastric adenocarcinoma (n=46) from the SNU cohort into the EAC-like or GCFB-like groups. The molecular characteristics between the EAC-like and GCFB-like groups were compared.
2022-02-06 | GSE126304 | GEO
Project description:Efforts to address the poor prognosis associated with esophageal adenocarcinoma (EAC) have been hampered by a lack of biomarkers to identify early disease and therapeutic targets. Despite extensive efforts to understand the somatic mutations associated with EAC over the past decade, a gap remains in understanding how the atlas of genomic aberrations in this cancer impacts the proteome and which somatic variants are of importance for the disease phenotype. We performed a quantitative proteomic analysis of 23 EACs and matched adjacent normal esophageal and gastric tissues. We explored the correlation of transcript and protein abundance using tissue-matched RNAseq and proteomic data from 7 patients and further integrated these data with a cohort of EAC RNA-seq data (n=264 patients), EAC whole-genome sequencing (n=454 patients) and external published datasets.
2024-08-10 | PXD042792 | Pride
Project description:<p>The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. When coupled to the five-year survival rate of only 15% for this disease, identification of new therapeutic targets for EAC is of great importance. Here, we analyze the mutational spectra identified from the whole genome sequencing of 16 EACs and complete exome sequencing of 149 EAC tumors and matched germline samples. We identify a novel mutation signature marked by high prevalence of A to C transversions at AA*(N) trinucleotides. Notably, the development of EAC is preceded by pathologic intestinal metaplasia of the lower esophagus, Barrett's esophagus, itself a response to injury from gastric-esophageal reflux disease (GERD). Thus, we hypothesize to represent these AA*(N) mutations to a novel signature of GERD-induced mutagenesis. Analysis of the exome data identified 26 genes subject to statistically significant recurrent mutation. Of these 26 genes, only TP53, CDKN2A, SMAD4, and PIK3CA had been previously implicated in EAC. Novel mutations include those targeting chromatin modifying factors and novel candidate contributors to EAC: SPG20, TLR4, ELMO1 and DOCK2. Of these, ELMO1 and DOCK2 are notably direct dimerization partners that act to activate Rac1 to enhance cellular invasiveness, thus generating new hypotheses about the potential for the Rac1 pathway to be a novel target for therapy of EAC.</p> <p>"Reprinted from 'Unraveling the mutational complexity of esophageal adenocarcinoma', with permission from Nature Genetics."</p>
| phs000598.v1.p1 | EGA
Project description:The aim of this project is to identify circulatory diagnostic glycoprotein biomarkers for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Serum samples from healthy, BE and EAC patients were screened using LeMBA-LC-MS/MS-GlycoSelector pipeline as described in the manuscript.
2015-09-25 | PXD002442 | Pride
Project description:Objectives: Long non-coding RNAs (lncRNAs) have been shown to play important roles in the development and progression of cancer. However, functional lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of esophageal adenocarcinoma (EAC) and its progression. Design: lncRNAs that are abnormally upregulated in EACs were identified by RNA-seq analysis, followed by quantitative RT-PCR (qRTPCR) validation using tissues from 31 EAC patients. Cell biological assays in combination with siRNA-mediated knockdown were performed in order to probe the functional relevance of these lncRNAs. Results: We discovered that a lncRNA, HNF1A-AS1, is markedly upregulated in human primary EACs relative to their corresponding normal esophageal tissues (mean fold change 7.2, p<0.01). We further discovered that HNF1A-AS1 knockdown significantly inhibited cell proliferation and anchorage independent growth, suppressed S-phase entry, and inhibited cell migration and invasion in multiple in vitro EAC models (p<0.05). A gene ontological analysis revealed that HNF1A-AS1 knockdown preferentially affected genes that are linked to assembly of chromatin and the nucleosome, a mechanism essential to cell cycle progression. The well-known cancer-related lncRNA, H19, was the gene most markedly inhibited by HNF1A-AS1 knockdown. Consistent to this finding, there was a significant positive correlation between HNF1A-AS1 and H19 expression in primary EACs (p<0.01). In order to identify novel oncogenic lncRNAs in esophageal adenocarcinogenesis, we carried out RNA-seq of a matched NE-BE-EAC tissue pair
2013-10-21 | E-GEOD-48240 | biostudies-arrayexpress
Project description:<p>The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. When coupled to the five-year survival rate of only 15% for this disease, identification of new therapeutic targets for EAC is of great importance. Here, we analyze the mutational spectra identified from the whole genome sequencing of 16 EACs and complete exome sequencing of 149 EAC tumors and matched germline samples. We identify a novel mutation signature marked by high prevalence of A to C transversions at AA*(N) trinucleotides. Notably, the development of EAC is preceded by pathologic intestinal metaplasia of the lower esophagus, Barrett's esophagus, itself a response to injury from gastric-esophageal reflux disease (GERD). Thus, we hypothesize to represent these AA*(N) mutations to a novel signature of GERD-induced mutagenesis. Analysis of the exome data identified 26 genes subject to statistically significant recurrent mutation. Of these 26 genes, only TP53, CDKN2A, SMAD4, and PIK3CA had been previously implicated in EAC. Novel mutations include those targeting chromatin modifying factors and novel candidate contributors to EAC: SPG20, TLR4, ELMO1 and DOCK2. Of these, ELMO1 and DOCK2 are notably direct dimerization partners that act to activate Rac1 to enhance cellular invasiveness, thus generating new hypotheses about the potential for the Rac1 pathway to be a novel target for therapy of EAC.</p> <p>"Reprinted from 'Unraveling the mutational complexity of esophageal adenocarcinoma', with permission from Nature Genetics."</p>
| phs000598 | dbGaP
Project description:Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that frequently develops from Barrettâs esophagus (BE), a premalignant pathological change occurring in the lower end of esophagus. To identify BE patients at high risk of malignant transformation is essential to the prevention of EAC. Although microRNA (miRNA) expression signatures have been associated with the etiology and prognosis of several types of cancers, their roles in the development of EAC have not been extensively evaluated. We analyzed the expression patterns of 470 human miRNAs using Agilent miRNA microarray in 32 disease/normal-paired tissues from 16 patients diagnosed with BE of either low or high grade dysplasia, or EAC
2010-05-16 | E-GEOD-16456 | biostudies-arrayexpress
Project description:Samples were obtained from 8 patients with Barrett's associated adenocarcinomas after transhiatal esophagectomy. Samples representative of the normal esophageal epithelium (N), Barrett’s esophagus (B) and esophageal adenocarcinomas (ADC) were obtained from every patient by experienced GI pathologists. RNA were extracted and samples were profiled for detection of genes differentially expressed in B and ADC relative to N and in ADC relative to B. Keywords: other
2004-11-18 | GSE1420 | GEO