Genomic and transcriptomic alterations associated with drug vulnerabilities and prognosis in adenocarcinoma at the gastroesophageal junction
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ABSTRACT:
PROVIDER: PRJNA670266 | ENA |
REPOSITORIES: ENA
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Project description:Adenocarcinoma at the gastroesophageal junction (ACGEJ) has dismal clinical outcomes and there are currently few specific effective therapies because of limited knowledge on its genomic and transcriptomic alterations. The present study investigates genomic and transcriptomic changes in ACGEJ from Chinese patients and analyzes their drug vulnerabilities and associations with the survival time. Here we show that the major genomic changes of Chinese ACGEJ patients are chromosome instability promoted tumorigenic focal copy-number variations and COSMIC Signature 17-featured single nucleotide variations. We provide a comprehensive profile of genetic changes that are potentially vulnerable to existing therapeutic agents and identify Signature 17-correlated IFN-α response pathway as a prognostic marker that might have practical value for clinical prognosis of ACGEJ. These findings further our understanding on the molecular biology of ACGEJ and may help develop more effective therapeutic strategies.
2020-11-09 | GSE159721 | GEO
Project description:We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas using 32k high-resolution array-based comparative genomic hybridization (aCGH) and 27k oligo gene expression arrays and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-q23, 5p15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction with upregulation in one quarter of the tumors. Gains/losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can be applied to adenocarcinomas of the distal esophagus and gastroesophageal junction alike. Three types of gastroesophageal adenocarcinomas; 7 distal esophageal (EA) tumors, 9 junctional (JA) and 7 proximal stomach cancers (GA) was genomically profiled using tiling 32k BAC-arrays. Two replicates of tumors IDs 1-EA-CGH (replicate 1-EA-CGH-2), 12-EA-CGH (replicate 12-EA-CGH-2) and 18-EA-CGH (replicate 18-EA-CGH-2). Reference samples consist of a pool of male DNA (Promega, Madison, WI, USA).
2010-06-24 | E-GEOD-22524 | biostudies-arrayexpress
Project description:We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas using 32k high-resolution array-based comparative genomic hybridization (aCGH) and 27k oligo gene expression arrays and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-q23, 5p15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction with upregulation in one quarter of the tumors. Gains/losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can be applied to adenocarcinomas of the distal esophagus and gastroesophageal junction alike.
2010-06-24 | GSE22524 | GEO
Project description:We aimed to genetically characterize adenocarcinomas in the gastroesophagel junction in relation to cancers in the esophagus and the stomach. In total 27 tumors was genetically profiled using gene expression array. Adenocarcinomas located in the gastroesophageal junction showed strong similarites with tumors in the distal esophagus, whereas different profiles were generated for tumors in the proximal stomach. Three types of gastroesophageal adenocarcinomas; 10 distal esophageal (EA) tumors, 9 junctional (JA) and 8 proximal stomach cancers (GA) was undergone differentially analysis based on gene expression profiles. One replicate of tumor ID 27_JA (replicate ID 27_JA_2) and one replicate of tumor ID 3-GA (replicate ID 3-GA-2). Reference samples consist of the Stratagene Universal Reference (10 cellines), commercially obtained from Stratagene, La Jolla, CA, USA.
2010-05-29 | E-GEOD-22050 | biostudies-arrayexpress
Project description:Adenocarcinoma at the gastroesophageal junction (ACGEJ) has dismal clinical outcomes, and there are currently few specific effective therapies because of limited knowledge on its genomic and transcriptomic alterations. The present study investigates genomic and transcriptomic changes in ACGEJ from Chinese patients and analyzes their drug vulnerabilities and associations with the survival time. Here we show that the major genomic changes of Chinese ACGEJ patients are chromosome instability promoted tumorigenic focal copy-number variations and COSMIC Signature 17-featured single nucleotide variations. We provide a comprehensive profile of genetic changes that are potentially vulnerable to existing therapeutic agents and identify Signature 17-correlated IFN-α response pathway as a prognostic marker that might have practical value for clinical prognosis of ACGEJ. These findings further our understanding on the molecular biology of ACGEJ and may help develop more effective therapeutic strategies.
| S-EPMC7705019 | biostudies-literature
Project description:We aimed to genetically characterize adenocarcinomas in the gastroesophagel junction in relation to cancers in the esophagus and the stomach. In total 27 tumors was genetically profiled using gene expression array. Adenocarcinomas located in the gastroesophageal junction showed strong similarites with tumors in the distal esophagus, whereas different profiles were generated for tumors in the proximal stomach.
2010-05-29 | GSE22050 | 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:Comprehensive molecular classification for adenocarcinoma of gastroesophageal junction between esophageal and gastric adenocarcinomas
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Project description:Gastric and esophagogastric junction adenocarcinoma with infrequent hypermethylation show poor prognosis
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Project description:A subgroup of patients with HER2-positive metastatic gastric and gastroesophageal junction cancers shows long-term response under trastuzumab maintenance monotherapy. Obviously, HER2 status alone is not able to identify these patients. We performed this study to identify potential new prognostic biomarkers for this long-term responding patient group. Tumor samples of 18 patients with HER2-positive metastatic gastric and gastroesophageal junction cancer who underwent trastuzumab treatment were retrospectively collected from multiple centers. Patients were divided into long-term responding (n=6) or fast-progression group (n=12) according to progression-free survival (PFS≥12 months vs PFS<12 months).We performed microarray-based gene expression analysis to investigate differences in immune cell populations between the patient groups.
2023-06-05 | GSE220917 | GEO