This SuperSeries is composed of the SubSeries listed below.
TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype.
Specimen part, Treatment
View SamplesThe aim of this study was to determine the effects of TGF at the premalignant stage of CRC development.
TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype.
Specimen part, Treatment
View SamplesColorectal cancer can be divided into four consensus molecular subtypes, which might associate with distinct precursor lesions. The aim of this study was to determine the subtype affiliation of two types of colorectal adenomas: tubular adenomas (TAs) and sessile serrated adenomas (SSAs) and to determine the activity of TGF signaling and the role of this cytokine in subtype affiliation.
TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CFTR is a tumor suppressor gene in murine and human intestinal cancer.
Age, Specimen part
View SamplesAnalysis of the cystic fibrosis gene Cftr in the colon and small intestine of Cftr-deficient murine model. The hypothesis was loss of Cftr altered expression of genes important in intestinal homeostasis and oncogenic signaling pathways. The results identified potential roles of Cftr in up- or down-regulating major gene clusters that belong to groups of immune response, ion channel, intestinal stem cell and other growth regulators. Overall design: The experiments were designed to analyze the role of Cftr-deficiency in tumorigenesis. The goal of this study was to identify genes and pathways associated with Cftr-deficiency in Apc wildtype and ApcMin mice. Total RNAs were isolated from mice, and subjected to deep sequencing, in duplicates, using Illumina HiSeq 2500. Samples that were sequenced in the same batch were analyzed in pair-wise using Tophat-Cuffdiff pipeline as outlined in Nature Protocol from Trapnell C. et al, 2012. The results indicated that Cftr-deficiency overlapped with genes and pathways involved in immune and inflammatory signaling, stem cell regulation, and Wnt/beta catenin signaling. Total RNA was isolated from multiple colon tumors and multiple small intestine tumors from Apc wildtype Cftr-deficient mice, ApcMin Cftr-deficient mice, and ApcMin Cftr wildtype mice. Total RNA was also obtained from Apc wildtype normal colon (epithelial cells) and normal duodenum (whole duodenum minus villi) from three Cftr wildtype and three Cftr-deficient mice. RNA Seq was then conducted on all samples with at least two replicates for each biological sample. Please note that 1) The 23 mice were processed in several batches, and two sequencing runs were carried out at two different dates. Â To control for the batch effect of sequencing, some samples were included in both runs (run1 and run2). 2) To reach the desired sequencing depth and to keep loading balance, each sample was split into halves, and sequenced on two lanes (L007 and L008 for run1, L006 and L007 for run2). therefore, for 11 samples, there are 4 technical replicates, including the 2-batches and 2-lane sequencing method. For the remaining 12 samples, there are 2 technical replicates, referring to the 2-lane sequencing. 3) some of the mice are heterozygous mutant of CFTR gene (CFTRhet), named as "CFTR knockdown".
CFTR is a tumor suppressor gene in murine and human intestinal cancer.
Age, Specimen part, Subject
View SamplesAnalysis of the cystic fibrosis gene Cftr in the colon and small intestine of Cftr-deficient murine model. The hypothesis was loss of Cftr altered expression of genes important in intestinal homeostasis and oncogenic signaling pathways. The results identified potential roles of Cftr in up- or down-regulating major gene clusters that belong to groups of immune response, ion channel, intestinal stem cell and other growth regulators.
CFTR is a tumor suppressor gene in murine and human intestinal cancer.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models.
Specimen part, Disease, Disease stage, Cell line, Subject
View SamplesColorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called Consensus Molecular Subtypes (CMS1-4), which each have a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed. This study was designed to determine the heterogeneity and identify the presence of CMSs in a large panel of CRC cell lines, primary cultures and patient-derived xenografts (PDX). We provide a repository encompassing this heterogeneity and moreover describe that a large part of the models can be robustly assigned to one of the four CMSs, independent of the stromal contribution. We subsequently validate our CMS stratification by functional analysis which for instance shows mesenchymal enrichment in CMS4 and metabolic dysregulation in CMS3. Finally, we observe a clear difference in sensitivity to chemotherapy-induced apoptosis, specifically between CMS2 and CMS4. This relates to the in vivo efficacy of chemotherapy, which delays outgrowth of CMS2, but not CMS4 xenografts. This indicates that molecular subtypes are faithfully modelled in the CRC cell cultures and PDXs, representing tumour cell intrinsic and stable features. This repository provides researchers with a platform to study CRC using the existing heterogeneity.
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models.
Specimen part, Disease, Disease stage, Subject
View SamplesColorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called Consensus Molecular Subtypes (CMS1-4), which each have a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed. This study was designed to determine the heterogeneity and identify the presence of CMSs in a large panel of CRC cell lines, primary cultures and patient-derived xenografts (PDX). We provide a repository encompassing this heterogeneity and moreover describe that a large part of the models can be robustly assigned to one of the four CMSs, independent of the stromal contribution. We subsequently validate our CMS stratification by functional analysis which for instance shows mesenchymal enrichment in CMS4 and metabolic dysregulation in CMS3. Finally, we observe a clear difference in sensitivity to chemotherapy-induced apoptosis, specifically between CMS2 and CMS4. This relates to the in vivo efficacy of chemotherapy, which delays outgrowth of CMS2, but not CMS4 xenografts. This indicates that molecular subtypes are faithfully modelled in the CRC cell cultures and PDXs, representing tumour cell intrinsic and stable features. This repository provides researchers with a platform to study CRC using the existing heterogeneity.
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models.
Specimen part, Disease, Disease stage, Subject
View SamplesColorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called Consensus Molecular Subtypes (CMS1-4), which each have a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed. This study was designed to determine the heterogeneity and identify the presence of CMSs in a large panel of CRC cell lines, primary cultures and patient-derived xenografts (PDX). We provide a repository encompassing this heterogeneity and moreover describe that a large part of the models can be robustly assigned to one of the four CMSs, independent of the stromal contribution. We subsequently validate our CMS stratification by functional analysis which for instance shows mesenchymal enrichment in CMS4 and metabolic dysregulation in CMS3. Finally, we observe a clear difference in sensitivity to chemotherapy-induced apoptosis, specifically between CMS2 and CMS4. This relates to the in vivo efficacy of chemotherapy, which delays outgrowth of CMS2, but not CMS4 xenografts. This indicates that molecular subtypes are faithfully modelled in the CRC cell cultures and PDXs, representing tumour cell intrinsic and stable features. This repository provides researchers with a platform to study CRC using the existing heterogeneity.
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models.
Disease, Disease stage, Cell line
View Samples