Consensus molecular subtype transition during progression of colorectal cancer.

Autor: van de Weerd S; Amsterdam UMC, University of Amsterdam, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam, The Netherlands.; Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.; Oncode Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Torang A; Amsterdam UMC, University of Amsterdam, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Zwager LW; Department of Gastroenterology and Hepatology, Amsterdam UMC, location AMC, Cancer Center Amsterdam and Amsterdam Gastroenterology & Metabolism, University of Amsterdam, Amsterdam, The Netherlands., Koelink PJ; Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Koster J; Amsterdam UMC, University of Amsterdam, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam, The Netherlands., Bastiaansen BA; Department of Gastroenterology and Hepatology, Amsterdam UMC, location AMC, Cancer Center Amsterdam and Amsterdam Gastroenterology & Metabolism, University of Amsterdam, Amsterdam, The Netherlands., Lammers V; Amsterdam UMC, University of Amsterdam, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Longobardi C; Amsterdam UMC, University of Amsterdam, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Roodhart JM; Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., van Krieken JH; Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands., Farina Sarasqueta A; Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Dekker E; Department of Gastroenterology and Hepatology, Amsterdam UMC, location AMC, Cancer Center Amsterdam and Amsterdam Gastroenterology & Metabolism, University of Amsterdam, Amsterdam, The Netherlands., Medema JP; Amsterdam UMC, University of Amsterdam, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2023 Nov; Vol. 261 (3), pp. 298-308. Date of Electronic Publication: 2023 Sep 08.
DOI: 10.1002/path.6176
Abstrakt: 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 region and the carcinoma region. In total, 24 patients who 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 (six out of seven) CMS3 precursor regions showed a shift to a different subtype in the carcinoma part of the lesion, which in four cases was classified as CMS4. In conclusion, our data indicate that CMS3 is related to a more indolent type of precursor lesion that less likely progresses to CRC and when this occurs, it is often associated 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 show 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 independently of such genetic changes. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
(© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)
Databáze: MEDLINE
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