Ontology highlight
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PROVIDER: PRJNA476415 | ENA |
REPOSITORIES: ENA
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Project description:Establishment of patient-derived tumor xenografts from Asian gastric adenocarcinoma is characterized by clonal selection and bias in molecular subtypes
| PRJNA475954 | ENA
Project description:establishment of patient derived tumor xenografts from Asian gastric adenocarcinoma is driven by molecular selection with implications for anticancer agent testing
| PRJEB26640 | ENA
Project description:Using data from high-density genomic profiling arrays, we investigated the profiles of somatic copy-number aberrations (SCNAs) in 659 gastric adenocarcinomas drawn approximately even numbers of Asian and Western patients with two goals in mind: (1) using the power of our large data set to detect new, and refine existing, regions of significantly recurring SCNAs; (2) determining if there exist fundamental differences in the manifestation of gastric adenocarcinoma in Asian versus Western patients that affect pattern of SCNAs. Among the 83 regions of significant alteration we indeed found some new targets in gastric adenocarcinoma such as the tumor suppressor gene SMARCA4 and proto-oncogene MYB, and additionally refined the boundaries of known significant regions. We found only slight differences in the overall copy number patterns between Asian and Western gastric adenocarcinoma patients indicating that the disease is fundamentally similar in both populations and the divergent clinical outcomes cannot be ascribed to different underlying SCNAs. The 111 copy number profiles contained in this archive are the previously unpublished portion of our study.
2017-04-15 | GSE77775 | GEO
Project description:We generated novel patient derived xenograft (PDX) and cell line -derived xenograft models for pancreatic ductal adenocarcinoma (PDAC) which reflect different molecular subtypes. Pancreatic ductal adenocarcinoma is currently the tumor with the fourth highest mortality rate. Recently, subtypes of PDAC have been reported by Collisson et al (Nat. Med. 17(4) 2011. DOI: 10.1038/nm.2344). However current fetal calf serum (FCS) cultured cell lines do not accurately model these subtypes. We thus generated novel serum-free cell lines derived from primary patient xenografts. We here analyse the gene-expression profiles of the xenografts and the derived cell lines. We show that indeed three different subtypes can be separated in our models based on gene-expression data. Further, we identify upregulation of a drug-detoxification pathway specifically in xenografts and cell lines of one of the subtypes. These models and data will help to better understand inter-patient heterogeneity in PDAC and identify novel drug targets and diagnostic markers.
2016-01-12 | E-MTAB-4029 | biostudies-arrayexpress
Project description:Gastric cancer is the most common cancer in Asia and most developing countries. To identify the molecular underpinnings of gastric cancer in the Asian population, we applied an RNA-sequencing approach to gastric tumor and noncancerous specimens to quantitatively characterize the entire transcriptome of gastric cancer (including mRNAs and microRNAs). A multi-layer analysis was then developed to identify multiple types of transcriptional aberrations associated with different stages of gastric cancer, including differentially expressed mRNAs, recurrent somatic mutations and key differentially expressed microRNAs. Through this approach, we identified the central metabolic regulator AMPK-α as a potential functional target in Asian gastric cancer. Further, we experimentally demonstrated the translational relevance of this gene as a potential therapeutic target for early-stage gastric cancer in Asian patients. Together, our findings not only provide a valuable information resource for identifying and elucidating the molecular mechanisms of Asian gastric cancer, but also represent a general integrative framework to develop more effective therapeutic targets.
2012-04-03 | GSE36968 | GEO
Project description:Gastric cancer is the most common cancer in Asia and most developing countries. To identify the molecular underpinnings of gastric cancer in the Asian population, we applied an RNA-sequencing approach to gastric tumor and noncancerous specimens to quantitatively characterize the entire transcriptome of gastric cancer (including mRNAs and microRNAs). A multi-layer analysis was then developed to identify multiple types of transcriptional aberrations associated with different stages of gastric cancer, including differentially expressed mRNAs, recurrent somatic mutations and key differentially expressed microRNAs. Through this approach, we identified the central metabolic regulator AMPK-M-NM-1 as a potential functional target in Asian gastric cancer. Further, we experimentally demonstrated the translational relevance of this gene as a potential therapeutic target for early-stage gastric cancer in Asian patients. Together, our findings not only provide a valuable information resource for identifying and elucidating the molecular mechanisms of Asian gastric cancer, but also represent a general integrative framework to develop more effective therapeutic targets. Using Life Technologies SOLiDM-bM-^DM-" sequencing platform, we performed transcriptome-wide profiling of gastric cancer samples from 30 anonymous, unrelated Asians of both sexes. Included were six noncancerous gastric tissue samples and 24 gastric tumor samples that represented stages I through IV of tumor development. From the WT-seq protocol we generated a WT-seq dataset of 2.1 billion 50-nt short reads from the 30 samples; Applying the second small RNA-seq protocol to 19 gastric tumor samples (5 of the original 24 yielded insufficient sample amounts) and 6 noncancerous gastric tissue samples resulted in a small RNA-seq dataset.
2012-04-03 | E-GEOD-36968 | biostudies-arrayexpress
Project description:The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastric adenocarcinomas from a Norwegian selection, compared to matched normal mucosa, and have related our findings to prognosis, survival and chronic Helicobacter pylori infection
2013-07-01 | E-MTAB-1440 | biostudies-arrayexpress
Project description:Background Worldwide, gastric cancer is the fourth most common malignancy and the most common cancer in East Asia. Development of targeted therapies for this disease has focused on a few known oncogenes but has had limited effects. Objective To determine oncogenic mechanisms and novel therapeutic targets specific for gastric cancer by identifying commonly dys-regulated genes from the tumors of both Asian-Pacific and Caucasian patients. Design We generated transcriptomic profiles of 22 Caucasian gastric cancer tumors and their matched non-cancerous samples, and performed an integrative analysis across different gastric cancer gene expression datasets. We examined the inhibition of commonly overexpressed oncogenes and their constituent signaling pathways by RNAi and/or pharmacologic inhibition. Results We found that HNF4α upregulation was a key signaling event in gastric tumors from both Caucasian and Asian patients, and HNF4α antagonism was antineoplastic. Perturbation experiments in GC tumor cell lines and xenograft models further demonstrated that HNF4α is downregulated by AMPKα signaling and the AMPK agonist metformin; blockade of HNF4α activity resulted in cyclin downregulation, cell cycle arrest, and tumor growth inhibition. HNF4α also regulated WNT signaling through its target gene WNT5A, a potential prognostic marker of diffuse type gastric tumors. Conclusions Our results indicate that HNF4α is a targetable oncoprotein in gastric cancer, is regulated by AMPK signaling through AMPKα, and resides upstream of WNT signaling. HNF4α may regulate “metabolic switch” characteristic of a general malignant phenotype and its target WNT5A has potential prognostic values. The AMPKα-HNF4α-WNT5A signaling cascade represents a potentially targetable pathway for drug development. Integrative analysis of Caucasian and Asian-Pacific gastric tumor expression datasets (including newly generated transcriptomic profiling of 22 tumors in this study) revealed a relatively small common sets of highly overexpressed genes.
2014-11-15 | E-GEOD-63288 | biostudies-arrayexpress
Project description:Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The extensive multiomics characterization of the xenografts demonstrated that PDX is a suitable model for preclinical studies, representing the diversity of the primary cancers. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The variable 'MultiOmicsClassification' indicates the resulting sample's group. 'CIMPclass' is the CpG island methylator phenotype as estimated from the methylation arrays analysis. In this dataset, Illumina Infinium HumanCode-24 BeadChips SNP arrays were used to analyze the DNA xenografts samples from pancreatic ductal adenocarcinoma.
2017-12-12 | E-MTAB-5006 | biostudies-arrayexpress