Molecular characterization of colorectal cancer related peritoneal metastatic disease

Kristiaan J. Lenos (), Sander Bach, Leandro Ferreira Moreno, Sanne Hoorn, Nina R. Sluiter, Sanne Bootsma, Felipe A. Vieira Braga, Lisanne E. Nijman, Tom Bosch, Daniel M. Miedema, Erik 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. Noesel, Onno Kranenburg, Jan Paul Medema, Jan Koster, Lianne Koens, Cornelis J. A. Punt, Pieter J. Tanis, Ignace H. Hingh, Maarten F. Bijlsma, Jurriaan B. Tuynman and Louis Vermeulen ()
Additional contact information
Kristiaan J. Lenos: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Sander Bach: Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam
Leandro Ferreira Moreno: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Sanne Hoorn: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Nina R. Sluiter: Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam
Sanne Bootsma: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Felipe A. Vieira Braga: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Lisanne E. Nijman: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Tom Bosch: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Daniel M. Miedema: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Erik Dijk: Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam
Bauke Ylstra: Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam
Ruth Kulicke: Celsius Therapeutics
Fred P. Davis: Celsius Therapeutics
Nicolas Stransky: Celsius Therapeutics
Gromoslaw A. Smolen: Celsius Therapeutics
Robert R. J. Coebergh van den Braak: Erasmus MC University Medical Center
Jan N. M. IJzermans: Erasmus MC University Medical Center
John W. M. Martens: Erasmus MC University Medical Center, Rotterdam, the Netherlands & Cancer Genomics Center
Sally Hallam: University of Birmingham
Andrew D. Beggs: University of Birmingham
Geert J. P. L. Kops: Oncode Institute
Nico Lansu: Oncode Institute
Vivian P. Bastiaenen: Amsterdam UMC location University of Amsterdam, Department of Surgery, Cancer Center Amsterdam
Charlotte E. L. Klaver: Amsterdam UMC location University of Amsterdam, Department of Surgery, Cancer Center Amsterdam
Maria C. Lecca: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Khalid El Makrini: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Clara C. Elbers: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Mark P. G. Dings: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Carel J. M. Noesel: Amsterdam UMC location University of Amsterdam, Department of Pathology, Cancer Center Amsterdam
Onno Kranenburg: University Medical Center Utrecht
Jan Paul Medema: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Jan Koster: Amsterdam UMC location University of Amsterdam, Department of Oncogenomics, Meibergdreef 9
Lianne Koens: Amsterdam UMC location University of Amsterdam, Department of Pathology, Cancer Center Amsterdam
Cornelis J. A. Punt: Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht University
Pieter J. Tanis: Amsterdam UMC location University of Amsterdam, Department of Surgery, Cancer Center Amsterdam
Ignace H. Hingh: Maastricht University
Maarten F. Bijlsma: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism
Jurriaan B. Tuynman: Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam
Louis Vermeulen: Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32198-z

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