Molecular characterization of colorectal cancer related peritoneal metastatic disease
Lenos, Kristiaan J.; Bach, Sander; Ferreira Moreno, Leandro; ten Hoorn, Sanne; Sluiter, Nina R.; Bootsma, Sanne; Vieira Braga, Felipe A.; Nijman, Lisanne E.; van den Bosch, Tom; Miedema, Daniel M.; van Dijk, Erik; Ylstra, Bauke; Kulicke, Ruth; Davis, Fred P.; Stransky, Nicolas; Smolen, Gromoslaw A.; Coebergh van den Braak, Robert R.J.; IJzermans, Jan N.M.; Martens, John W.M.; Hallam, Sally; Beggs, Andrew D.; Kops, Geert J.P.L.; Lansu, Nico; Bastiaenen, Vivian P.; Klaver, Charlotte E.L.; Lecca, Maria C.; El Makrini, Khalid; Elbers, Clara C.; Dings, Mark P.G.; van Noesel, Carel J.M.; Kranenburg, Onno; Medema, Jan Paul; Koster, Jan; Koens, Lianne; Punt, Cornelis J.A.; Tanis, Pieter J.; de Hingh, Ignace H.; Bijlsma, Maarten F.; Tuynman, Jurriaan B.; Vermeulen, Louis
(2022) Nature Communications, volume 13, issue 1
(Article)
Abstract
A significant proportion of colorectal cancer (CRC) patients develop peritoneal metastases (PM) in the course of their disease. PMs are associated with a poor quality of life, significant morbidity and dismal disease outcome. To improve care for this patient group, a better understanding of the molecular characteristics of CRC-PM is
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required. Here we present a comprehensive molecular characterization of a cohort of 52 patients. This reveals that CRC-PM represent a distinct CRC molecular subtype, CMS4, but can be further divided in three separate categories, each presenting with unique features. We uncover that the CMS4-associated structural protein Moesin plays a key role in peritoneal dissemination. Finally, we define specific evolutionary features of CRC-PM which indicate that polyclonal metastatic seeding underlies these lesions. Together our results suggest that CRC-PM should be perceived as a distinct disease entity.
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Keywords: General Chemistry, General Biochemistry,Genetics and Molecular Biology, General, General Physics and Astronomy
ISSN: 2041-1723
Publisher: Nature Publishing Group
Note: Funding Information: This work is supported by Oncode Institute, The New York Stem Cell Foundation, grants from KWF (10529 to L.V. and 13435 to M.F.B.), the European Research Council (ERC-StG 638193) and ZonMw (Vidi 016.156.308) to L.V. L.V. is a New York Stem Cell Foundation – Robertson Investigator. Publisher Copyright: © 2022, The Author(s).
(Peer reviewed)
