Next generation sequencing of FFPE human colon cancer samples for validation of ColoType consensus molecular subtype (CMS) assay
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ABSTRACT:
PROVIDER: PRJNA639303 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12009328_1.fastq.gz | Fastqsanger.gz | |||
| SRR12009328_2.fastq.gz | Fastqsanger.gz | |||
| SRR12009329_1.fastq.gz | Fastqsanger.gz | |||
| SRR12009329_2.fastq.gz | Fastqsanger.gz | |||
| SRR12009330_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: To validate the novel ColoType assay for computing consensus molecular subtypes of colon cancer tumor samples Method: Whole-genome RNA-sequencing of colon cancer samples from formalin-fixed paraffin-embedded (FFPE) provided data for consensus molecular subtyping samples using multiple independent methods, including the novel ColoType method. A custom Illumina AmpliSeq library was also used to implement ColoType on these samples by targeted RNA-sequencing. Results: Multiple independent methods for computing CMS subtypes for FFPE colon cancer samples have widespread agreement with ColoType assay.
2020-07-27 | GSE152430 | GEO
Project description:The consensus molecular subtype (CMS) classification divides colorectal cancer (CRC) into four distinct subtypes based on RNA-expression profiles. The biological differences between CMSs are already present in CRC precursor lesions, but not all CMSs pose the same risk of malignant transformation. To fully understand the path to malignant transformation and to determine whether CMS is a fixed entity during progression, genomic and transcriptomic data from two regions of the same CRC lesion were compared: the precursor and carcinoma region. In total, 24 patients that underwent endoscopic removal of T1-2 CRC were included. Regions were subtyped for CMS and DNA mutation analysis was performed. Additionally, a set of 85 benign adenomas was CMS subtyped. This analysis revealed that almost all benign adenomas were classified as CMS3 (91.8%). In contrast, CMS2 was the most prevalent subtype in precursor regions (66.7%), followed by CMS3 (29.2%). CMS4 was absent in precursor lesions and originated at the carcinoma stage. Importantly, CMS switching occurred in a substantial number of cases and almost all (6 out of 7) CMS3 precursor regions showed a shift to a different subtype in the carcinoma part of the lesion, which in 4 cases was classified as CMS4. In conclusion, our data indicate that CMS3 is related to a more indolent type of precursor lesions that less likely progresses to CRC and when this occurs it often associates with a subtype change that includes the more aggressive mesenchymal CMS4. In contrast, an acquired CMS2 signature appeared to be rather fixed during early CRC development. Combined our data shows that subtype changes occur during progression and that CMS3 switching is related to changes in the genomic background through acquisition of a novel driver mutation (TP53) or selective expansion of a clone, but also occurred independent of such genetic changes.
2023-07-13 | GSE237247 | GEO
Project description:The consensus molecular subtype (CMS) classification divides colorectal cancer (CRC) into four distinct subtypes based on RNA-expression profiles. The biological differences between CMSs are already present in CRC precursor lesions, but not all CMSs pose the same risk of malignant transformation. To fully understand the path to malignant transformation and to determine whether CMS is a fixed entity during progression, genomic and transcriptomic data from two regions of the same CRC lesion were compared: the precursor and carcinoma region. In total, 24 patients that underwent endoscopic removal of T1-2 CRC were included. Regions were subtyped for CMS and DNA mutation analysis was performed. Additionally, a set of 85 benign adenomas was CMS subtyped. This analysis revealed that almost all benign adenomas were classified as CMS3 (91.8%). In contrast, CMS2 was the most prevalent subtype in precursor regions (66.7%), followed by CMS3 (29.2%). CMS4 was absent in precursor lesions and originated at the carcinoma stage. Importantly, CMS switching occurred in a substantial number of cases and almost all (6 out of 7) CMS3 precursor regions showed a shift to a different subtype in the carcinoma part of the lesion, which in 4 cases was classified as CMS4. In conclusion, our data indicate that CMS3 is related to a more indolent type of precursor lesions that less likely progresses to CRC and when this occurs it often associates with a subtype change that includes the more aggressive mesenchymal CMS4. In contrast, an acquired CMS2 signature appeared to be rather fixed during early CRC development. Combined our data shows that subtype changes occur during progression and that CMS3 switching is related to changes in the genomic background through acquisition of a novel driver mutation (TP53) or selective expansion of a clone, but also occurred independent of such genetic changes.
2023-07-13 | GSE237248 | GEO
Project description:Tumor heterogeneity is a major challenge to the treatment of colorectal cancer (CRC). Recently, a transcriptome-based classification was developed, segregating CRC into four consensus molecular subtypes (CMS) with distinct biological and clinical characteristics. Here, we applied the CMS classification on CRC cell lines to identify novel subtype-specific drug vulnerabilities. We combined publicly available transcriptome data from multiple resources to assign 159 CRC cell lines to CMS. By integrating results from large scale drug screens, we discovered that CMS1 cancer is highly vulnerable to the survivin suppressor YM155. We confirmed our results using an independent panel of CRC cell lines and demonstrate a 100-fold higher sensitivity of CMS1 lines. This vulnerability was specific to YM155 and not observed for commonly used chemotherapeutic agents. In CMS1 cancer, low concentrations of YM155 induced apoptosis and expression signatures associated with NFkappaB and ER stress mediated apoptosis signaling. Using a genome-wide CRISPR/Cas9 screen, we discovered a novel role of genes involved in LDL-receptor recycling as modulators of YM155 response in CMS1 CRC. Our work shows that combining drug response data with CMS classification in cell lines can reveal specific vulnerabilities and propose YM155 as novel CMS1 specific drug.
2018-07-03 | GSE116529 | GEO
Project description:Tumor heterogeneity is a major challenge to the treatment of colorectal cancer (CRC). Recently, a transcriptome-based classification was developed, segregating CRC into four consensus molecular subtypes (CMS) with distinct biological and clinical characteristics. Here, we applied the CMS classification on CRC cell lines to identify novel subtype-specific drug vulnerabilities. We combined publicly available transcriptome data from multiple resources to assign 159 CRC cell lines to CMS. By integrating results from large scale drug screens, we discovered that CMS1 cancer is highly vulnerable to the survivin suppressor YM155. We confirmed our results using an independent panel of CRC cell lines and demonstrate a 100-fold higher sensitivity of CMS1 lines. This vulnerability was specific to YM155 and not observed for commonly used chemotherapeutic agents. In CMS1 cancer, low concentrations of YM155 induced apoptosis and expression signatures associated with NFkappaB and ER stress mediated apoptosis signaling. Using a genome-wide CRISPR/Cas9 screen, we discovered a novel role of genes involved in LDL-receptor recycling as modulators of YM155 response in CMS1 CRC. Our work shows that combining drug response data with CMS classification in cell lines can reveal specific vulnerabilities and propose YM155 as novel CMS1 specific drug. We performed expression profiling experiments in order to validate molecular subtypes for selected cell lines
2018-07-03 | GSE116528 | GEO
Project description:Consensus molecular subtype transition during progression of colorectal cancer
| PRJNA994462 | ENA
Project description:The Colorectal Cancer Subtyping Consortium established four Consensus Molecular Subtypes (CMS) in colorectal cancer: CMS1 (microsatellite-instability [MSI], Immune), CMS2 (Canonical, epithelial), CMS3 (Metabolic), and CMS4 (Mesenchymal). However, in the clinical practice only patients with MSI tumors have experienced a change in the management of their disease. Proteomics has experimented significant technical advances with the implementation of data-independent acquisition (DIA) as the gold-standard for the analysis of large cohort of patients, providing a dynamic framework of the disease and direct information about the effectors of the biological processes. The aim of this study is the characterization of the proteome of colon cancer CMS by DIA–based proteomics and expand the utility of CMS in the clinical practice. CMS were assigned and differences in the protein profiles between CMS were defined and evaluated using a Systems Biology approach. One hundred fifty-eight paraffin samples from colon cancer patients with stage II-III disease treated with adjuvant chemotherapy were analyzed. After applying quality criteria, 1,940 identified and quantified proteins were used for the analyses. CMS1 had an overexpression of proteins related to immune system, specifically neutrophils, phagocytosis and antimicrobial response, and a glycolytic profile. CMS3 had an overexpression of proteins related to metabolic pathways, while CMS2 showed an intermediate protein profile between CMS1-3, but with a characteristic profile regarding translation, adhesion, and mitochondria and metabolism biological processes. Two proteomics subtypes within CMS2 with different protein characteristics and prognosis were identified. CMS4 was the most different group with an overexpression of proteins related to angiogenesis, extracellular matrix, focal adhesion, and complement activation. In conclusion, DIA LC-MS/MS proteomics characterization of CRC CMS established new features for each CMS, such as a higher mitochondrial activity in CMS2 or an overexpression of proteins related to phagocytosis in CMS1, but also confirmed previous findings established using transcriptomics such as an overexpression of proteins related to angiogenesis in CMS4. In this CMS4 subtype, several adhesion-related proteins suggested a high metastatic profile and a possible chemoresistance that may explain the worse prognosis of this subtype. CMS1 was characterized as immune and glycolitic-active subtype, being the combination of immunotherapy and glycolytic inhibitors a possible therapeutic strategy. Additionally, two different CMS2 proteomics-based subtypes with different prognosis and possible therapeutic targets were identified. These proccesses could be used as therapeutic targets in the future.
2024-09-30 | PXD044935 | Pride
Project description:162 FFPE samples, representing six different tumour types, were profiled in triplicate across three independent laboratories. OncoScan¬ FFPE assay data was then analysed for reproducibility of genome-wide copy number, loss of heterozygosity and somatic mutations.
2015-02-18 | E-MTAB-2914 | biostudies-arrayexpress
Project description:Consensus molecular subtype transition during progression of colorectal cancer [NanoClassifier Gene Set]
| PRJNA994465 | ENA
Project description:This work presents a novel Consensus Molecular Subtypes (CMS) classifier for colorectal cancer (CRC), optimized for degraded RNA stemming from clinical formalin-fixed paraffin-embedded tissue samples.
2024-05-22 | GSE267010 | GEO