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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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
Number of pages14
JournalNature Communications
Issue number1
Publication statusPublished - 4 Aug 2022

Bibliographical note

© 2022. The Author(s).


  • Colorectal Neoplasms/pathology
  • Humans
  • Neoplasms, Second Primary
  • Peritoneal Neoplasms/genetics
  • Peritoneum/metabolism
  • Quality of Life


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