Avastin and Tarceva for Upper Gastrointestinal Cancers
Ontology highlight
ABSTRACT:
DISEASE(S): Gallbladder Neoplasms,Gallbladder Cancer,Histologically Or Cytologically Verified Upper Gastro-intestinal Carcinoma, Including Carcinomas Of The Esophagus, Cardia, Stomac, Pancreas, Gall Bladder, And Bile Ducts Of The Following Histological Subtypes: Adenocarcinoma, Planocellular Or Squamous Cell Carcinoma, And Anaplastic/high-grade Or Undifferentiated Carcinoma,Cholangiocarcinoma
PROVIDER: 2030763 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Using data from high-density genomic profiling arrays, we describe the profiles of somatic copy-number aberrations (SCNAs) in 486 adenocarcinomas across all three major digestive organs, including 296 gastric and esophageal cancers. This analysis revealed that although patterns of broad, chromosome arm-level alterations are similar across the three types of adenocarcinoma, focal genomic amplifications are substantially more prevalent in gastric/esophageal adenocarcinoma. A statistical analysis identified 64 regions of significantly recurrent amplification and deletion, including those shared across these tumors and those uniquely significant in adenocarcinomas from a single organ. Among significantly amplified genes are those encoding therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, events noted in 14% of colorectal adenocarcinomas and 37% of gastric/esophageal tumors suggesting that analysis of genomic amplification will be a critical source of biomarkers to guide therapies in upper gastrointestinal adenocarcinomas. While many of the other significant loci of amplifications implicate genes recognized to play roles in gastrointestinal and other cancers, other loci point to regions that may harbor novel genes contributing to these cancers. One such event is a recurrent focal deletion present in 15% of esophageal adenocarcinomas, which we narrow to a single likely target, the Runt transcription factor subunit RUNX1. Indeed, reintroduction of RUNX1 into a cell model with this deletion inhibited anchorage-independent growth. Overall, these results demonstrate genomic features common to these tumors and identify key differences that reflect distinctive biology and potential opportunities for therapeutic intervention.
2012-09-04 | GSE36458 | GEO
Project description:Using data from high-density genomic profiling arrays, we describe the profiles of somatic copy-number aberrations (SCNAs) in 486 adenocarcinomas across all three major digestive organs, including 296 gastric and esophageal cancers. This analysis revealed that although patterns of broad, chromosome arm-level alterations are similar across the three types of adenocarcinoma, focal genomic amplifications are substantially more prevalent in gastric/esophageal adenocarcinoma. A statistical analysis identified 64 regions of significantly recurrent amplification and deletion, including those shared across these tumors and those uniquely significant in adenocarcinomas from a single organ. Among significantly amplified genes are those encoding therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, events noted in 14% of colorectal adenocarcinomas and 37% of gastric/esophageal tumors suggesting that analysis of genomic amplification will be a critical source of biomarkers to guide therapies in upper gastrointestinal adenocarcinomas. While many of the other significant loci of amplifications implicate genes recognized to play roles in gastrointestinal and other cancers, other loci point to regions that may harbor novel genes contributing to these cancers. One such event is a recurrent focal deletion present in 15% of esophageal adenocarcinomas, which we narrow to a single likely target, the Runt transcription factor subunit RUNX1. Indeed, reintroduction of RUNX1 into a cell model with this deletion inhibited anchorage-independent growth. Overall, these results demonstrate genomic features common to these tumors and identify key differences that reflect distinctive biology and potential opportunities for therapeutic intervention.
2012-09-04 | GSE36459 | GEO
Project description:Using data from high-density genomic profiling arrays, we describe the profiles of somatic copy-number aberrations (SCNAs) in 486 adenocarcinomas across all three major digestive organs, including 296 gastric and esophageal cancers. This analysis revealed that although patterns of broad, chromosome arm-level alterations are similar across the three types of adenocarcinoma, focal genomic amplifications are substantially more prevalent in gastric/esophageal adenocarcinoma. A statistical analysis identified 64 regions of significantly recurrent amplification and deletion, including those shared across these tumors and those uniquely significant in adenocarcinomas from a single organ. Among significantly amplified genes are those encoding therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, events noted in 14% of colorectal adenocarcinomas and 37% of gastric/esophageal tumors suggesting that analysis of genomic amplification will be a critical source of biomarkers to guide therapies in upper gastrointestinal adenocarcinomas. While many of the other significant loci of amplifications implicate genes recognized to play roles in gastrointestinal and other cancers, other loci point to regions that may harbor novel genes contributing to these cancers. One such event is a recurrent focal deletion present in 15% of esophageal adenocarcinomas, which we narrow to a single likely target, the Runt transcription factor subunit RUNX1. Indeed, reintroduction of RUNX1 into a cell model with this deletion inhibited anchorage-independent growth. Overall, these results demonstrate genomic features common to these tumors and identify key differences that reflect distinctive biology and potential opportunities for therapeutic intervention. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from 87 cancer DNAs derived from primary tumor tissues, as well as from DNA obtained from 1,480 normal DNA samples. Signal intensities were normalized to raw copy number estimates using the tangent normalization method, as described in Beroukhim et al., In Press and Mermel et al., In preparation. The 250K Sty data from this submission were combined with data for 128 colon adenocarcinomas (Firestein et al, Nature 2008) and segmented using GLAD. These segmented data were then combined with segmented SNP 6.0 data for 62 colon, 97 gastric and 112 esophageal adenocarcinomas using common markers to anchor the segments. Data analysis across samples was performed using this GISTIC 2.0 algorithm (Mermel C et al, Genome Biology 2011).
2012-09-04 | E-GEOD-36459 | biostudies-arrayexpress
Project description:Using data from high-density genomic profiling arrays, we describe the profiles of somatic copy-number aberrations (SCNAs) in 486 adenocarcinomas across all three major digestive organs, including 296 gastric and esophageal cancers. This analysis revealed that although patterns of broad, chromosome arm-level alterations are similar across the three types of adenocarcinoma, focal genomic amplifications are substantially more prevalent in gastric/esophageal adenocarcinoma. A statistical analysis identified 64 regions of significantly recurrent amplification and deletion, including those shared across these tumors and those uniquely significant in adenocarcinomas from a single organ. Among significantly amplified genes are those encoding therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, events noted in 14% of colorectal adenocarcinomas and 37% of gastric/esophageal tumors suggesting that analysis of genomic amplification will be a critical source of biomarkers to guide therapies in upper gastrointestinal adenocarcinomas. While many of the other significant loci of amplifications implicate genes recognized to play roles in gastrointestinal and other cancers, other loci point to regions that may harbor novel genes contributing to these cancers. One such event is a recurrent focal deletion present in 15% of esophageal adenocarcinomas, which we narrow to a single likely target, the Runt transcription factor subunit RUNX1. Indeed, reintroduction of RUNX1 into a cell model with this deletion inhibited anchorage-independent growth. Overall, these results demonstrate genomic features common to these tumors and identify key differences that reflect distinctive biology and potential opportunities for therapeutic intervention. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from 271 cancer DNAs derived from primary tissues, as well as from DNA obtained from 60 normal DNA samples. Signal intensities were normalized to raw copy number estimates using the tangent normalization method, as described in Beroukhim et al., In Press and Mermel et al., In preparation. The SNP 6.0 data from this submission were segmented using CBS. These segmented data were then combined with segmented Affymetrix 250K Sty data for 128 colon, 13 gastric and 74 esophageal adenocarcinomas using common markers to anchor the segments. Data analysis across samples was performed using this GISTIC 2.0 algorithm (Mermel C et al, Genome Biology 2011).
2012-09-04 | E-GEOD-36458 | biostudies-arrayexpress
Project description:Gastro-esophageal adenocarcinomas (GEAs) are aggressive cancers and multiple trials of targeted therapies recently failed to improve survival in these tumors. Intratumor heterogeneity (ITH) is suspected to contribute to poor outcomes. Here we investigate the degree of ITH in multiple primary and metastatic regions of gastric adenocarcinoma tumours. ITH increased significantly with lymph node metastasis formation and subclonal aberrations activating the Mitogen Activated Protein Kinase (MAPK)-pathway were significantly enriched in nodal metastases. This shows that selection pressures in the lymph node ecosystem differ from those in the primary tumor, leading to evolutionary convergence of distinct tumors when they spread to lymph nodes.
2019-09-18 | GSE93583 | GEO
Project description:In this study, we used RNA sequencing to characterize esophageal progenitors following activation of the hedgehog (HH) pathway in vivo. We observed two main fates following activation of the HH pathway in the squamous epithelium: one population is in an intermediate state between squamous and columnar epithelium, and another achieves a full columnar conversion. We compared these 2 populations to different FACS sorted epithelial cells from different tissues of the gastro-intestinal tract (adult esophagus, embryonic esophagus, transition epithelium from the stomach, corpus of the stomach and small intestine). Our results suggest a multistep process in which esophageal progenitors first turn on a transcriptomic program that resembles the one from embryonic esophagus, then, a subset of these dedifferentiated cells can turn on a columnar differentiation program that shares similarities with intestinal cells. Collectively, these data demonstrate that some esophageal cells can be reprogrammed to generate columnar cells in vivo.
2021-04-20 | GSE148874 | GEO
Project description:Cancers of the gastrointestinal tract including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia are common comorbidities of obesity. Excessive delivery of macronutrients to the cells lining the gut can increase one’s risk for these cancer by inducing imbalances in the rate of intestinal stem cell proliferation vs. differentiation, which can produce polyps and other aberrant growths. We demonstrate that serine palmitoyltransferase (SPT), which diverts dietary fatty and amino acids into the sphingolipid biosynthesis pathway, is a critical modulator of intestinal stem cell homeostasis. SPT and other enzymes in the biosynthetic pathway are upregulated in human colon tumors. These enzymes produce sphingolipids that serve as pro-stemness signals that stimulate peroxisome-proliferator activated receptor alpha (PPARa)-mediated induction of fatty acid binding protein-1. This increases fatty acid uptake and oxidation and enhances the stemness program. Serine palmitoyltransferase thus serves as a critical link between dietary macronutrients, epithelial regeneration, and cancer risk.
2022-11-01 | GSE188675 | GEO
Project description:Cancers of the gastrointestinal tract including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia are common comorbidities of obesity. Excessive delivery of macronutrients to the cells lining the gut can increase one’s risk for these cancer by inducing imbalances in the rate of intestinal stem cell proliferation vs. differentiation, which can produce polyps and other aberrant growths. We demonstrate that serine palmitoyltransferase (SPT), which diverts dietary fatty and amino acids into the sphingolipid biosynthesis pathway, is a critical modulator of intestinal stem cell homeostasis. SPT and other enzymes in the biosynthetic pathway are upregulated in human colon tumors. These enzymes produce sphingolipids that serve as pro-stemness signals that stimulate peroxisome-proliferator activated receptor alpha (PPARa)-mediated induction of fatty acid binding protein-1. This increases fatty acid uptake and oxidation and enhances the stemness program. Serine palmitoyltransferase thus serves as a critical link between dietary macronutrients, epithelial regeneration, and cancer risk.
2022-11-01 | GSE188674 | 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