Molecular characterization of colorectal cancer related peritoneal metastatic disease

Author:

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

Abstract

AbstractA 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.

Funder

KWF Kankerbestrijding

ZonMw

This work is supported by the Academic Medical Center (Amsterdam), The New York Stem Cell Foundation, L.V. is a New York Stem Cell Foundation – Robertson Investigator.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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