 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 13, 2023 |
| Title |
Consensus molecular subtype transition during progression of colorectal cancer [Tumor Signaling 360™ Panel] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
|
| |
|
| Overall design |
This study retrospectively selected patients who underwent endoscopic resection for early-stage colorectal cancer (CRC) at the Amsterdam University Medical Centers, location AMC, between 2016 and 2021. Exclusions were made for patients with hereditary CRC predisposition, inflammatory bowel disease history, neoadjuvant treatment evidence, or piecemeal resection. Informed consent was obtained, and the study followed the guidelines of the Declaration of Helsinki and the Netherlands Code of Conduct. Pathology review involved collecting haematoxylin-eosin (H&E) slides and formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks, which were reviewed by two expert pathologists. The amount of carcinoma and precursor tissue was assessed, and specimens with sufficient tissue for RNA and DNA extraction were selected. The precursor adenoma region was categorized based on dysplasia level and morphology. RNA and DNA were extracted from the same tissue sections using the AllPrep FFPE DNA/RNA kit (Qiagen, Hilden, Germany) according to manufacturer’s instructions. RNA quantity and quality were measured using NanoDrop2000 (Thermo Fisher Scientific, Waltham, MA, USA) and Tapestation (Agilent Technologies, Santa Clara, CA, USA). DNA quantity was assessed with a Qubit Fluorometer (Thermo Fisher Scientific, Waltham, MA, USA).
|
| |
|
| Contributor(s) |
Weerd S, Torang A, Medema JP |
| Citation(s) |
37681286 |
| |
| Submission date |
Jul 13, 2023 |
| Last update date |
Oct 16, 2023 |
| Contact name |
Arezo Torang |
| E-mail(s) |
a.torang@amsterdamumc.nl
|
| Organization name |
Amsterdam UMC
|
| Street address |
Meibergdreef 9
|
| City |
Amsterdam |
| ZIP/Postal code |
1105 AZ |
| Country |
Netherlands |
| |
|
| Platforms (1) |
| GPL33582 |
nCounter® NanoString Tumor Signaling 360™ Panel |
|
| Samples (24)
|
|
| This SubSeries is part of SuperSeries: |
| GSE237249 |
Consensus molecular subtype transition during progression of colorectal cancer |
|
| Relations |
| BioProject |
PRJNA994464 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE237248_RAW.tar |
240.0 Kb |
(http)(custom) |
TAR (of RCC) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...