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Consensus molecular subtype transition during progression of colorectal cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE237249 | GEO | 2023/07/13

REPOSITORIES: GEO

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Consensus molecular subtype transition during progression of colorectal cancer [NanoClassifier Gene Set]

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

Consensus molecular subtype transition during progression of colorectal cancer [Tumor Signaling 360™ Panel]

2023-07-13 | GSE237248 | GEO

Consensus molecular subtype classification of colorectal adenomas.

Project description: Not available

| S-EPMC6221003 | biostudies-literature

Molecular features of subtype-specific progression from ductal carcinoma in situ to invasive breast cancer

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-07-07 | E-GEOD-59248 | biostudies-arrayexpress

Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer.

Project description: Not available

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Consensus Molecular Subtypes of colorectal cancer are recapitulated in in vitro and in vivo models

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-12-01 | GSE100550 | GEO

TGFÎ² signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-06-01 | E-GEOD-79462 | biostudies-arrayexpress

AKT dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer subtype

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-07-29 | GSE136257 | GEO

Identification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer.

Project description: Not available

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Consensus Molecular Subtype predicts differential vulnerability of colorectal cancer to the survivin suppressant YM155 II

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

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