Molecular characterization of colorectal cancer related peritoneal metastatic disease
Kristiaan Lenos, Sander Bach, Leandro F. Moreno, Sanne ten Hoorn, Nina R. Sluiter, Sanne Bootsma, Felipe A. Vieira Braga, Lisanne E. Nijman, Tom van den Bosch, Daniël 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 Hallam, Andrew 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 Köster, Lianne Koens, Cornelis J.A. Punt, Pieter J. Tanis, Ignace H. J. T. de Hingh, Maarten F. Bijlsma, Jurriaan B. Tuynman, Louis Vermeulen
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.