Molecular characterization of colorectal cancer related peritoneal metastatic disease

Kristiaan J. Lenos, Sander Bach, Leandro Ferreira Moreno, Sanne ten Hoorn, Nina R. Sluiter, Sanne Bootsma, Felipe A. Vieira Braga, Lisanne E. Nijman, Tom van den Bosch, Daniel M. Miedema, Erik van Dijk, Bauke Ylstra, Ruth Kulicke, Fred P. Davis, Nicolas Stransky, Gromoslaw A. Smolen, Robert R. J. Coebergh van den Braak, Jan N. M. IJzermans, John W. M. Martens, Sally HallamAndrew D. Beggs, Geert J. P. L. Kops, Nico Lansu, Vivian P. Bastiaenen, Charlotte E. L. Klaver, Maria C. Lecca, Khalid el Makrini, Clara C. Elbers, Mark P. G. Dings, Carel J. M. van Noesel, Onno Kranenburg, Jan Paul Medema, Jan Koster, Lianne Koens, Cornelis J. A. Punt, Pieter J. Tanis, Ignace H. de Hingh, Maarten F. Bijlsma, Jurriaan B. Tuynman, Louis Vermeulen

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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 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.
Original languageEnglish
Article number4443
JournalNature communications
Volume13
Issue number1
DOIs
Publication statusPublished - 1 Dec 2022

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