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 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 Koster; Lianne Koens; Cornelis J A Punt; Pieter J Tanis; Ignace H de Hingh; Maarten F Bijlsma; Jurriaan B Tuynman; Louis Vermeulen

doi:10.1038/s41467-022-32198-z

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 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 Koster, Lianne Koens, Cornelis J A Punt, Pieter J Tanis, Ignace H de Hingh, Maarten F Bijlsma, Jurriaan B Tuynman, Louis Vermeulen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Article number	4443
Number of pages	14
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-32198-z
Publication status	Published - 4 Aug 2022

Keywords

Colorectal Neoplasms/pathology
Humans
Neoplasms, Second Primary
Peritoneal Neoplasms/genetics
Peritoneum/metabolism
Quality of Life
ERM PROTEINS
INSTABILITY
PROGNOSIS
COLON
PREVALENCE
IDENTIFICATION
FAMILY
BRAF MUTATION
CARCINOMATOSIS
KRAS

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Lenos, K. J., Bach, S., Ferreira Moreno, L., Ten Hoorn, S., Sluiter, N. R., Bootsma, S., Vieira Braga, F. A., Nijman, L. E., van den Bosch, T., Miedema, D. M., van Dijk, E., Ylstra, B., Kulicke, R., Davis, F. P., Stransky, N., Smolen, G. A., Coebergh van den Braak, R. R. J., IJzermans, J. N. M., Martens, J. W. M., ... Vermeulen, L. (2022). Molecular characterization of colorectal cancer related peritoneal metastatic disease. Nature Communications, 13(1), Article 4443. https://doi.org/10.1038/s41467-022-32198-z

@article{a5537107cb554e899ea893466b767265,

title = "Molecular characterization of colorectal cancer related peritoneal metastatic disease",

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.",

keywords = "Colorectal Neoplasms/pathology, Humans, Neoplasms, Second Primary, Peritoneal Neoplasms/genetics, Peritoneum/metabolism, Quality of Life, ERM PROTEINS, INSTABILITY, PROGNOSIS, COLON, PREVALENCE, IDENTIFICATION, FAMILY, BRAF MUTATION, CARCINOMATOSIS, KRAS",

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

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

month = aug,

day = "4",

doi = "10.1038/s41467-022-32198-z",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Lenos, KJ, Bach, S, Ferreira Moreno, L, Ten Hoorn, S, Sluiter, NR, Bootsma, S, Vieira Braga, FA, Nijman, LE, van den Bosch, T, Miedema, DM, van Dijk, E, Ylstra, B, Kulicke, R, Davis, FP, Stransky, N, Smolen, GA, Coebergh van den Braak, RRJ, IJzermans, JNM, Martens, JWM, Hallam, S, Beggs, AD, Kops, GJPL, Lansu, N, Bastiaenen, VP, Klaver, CEL, Lecca, MC, El Makrini, K, Elbers, CC, Dings, MPG, van Noesel, CJM, Kranenburg, O, Medema, JP, Koster, J, Koens, L, Punt, CJA, Tanis, PJ, de Hingh, IH, Bijlsma, MF, Tuynman, JB & Vermeulen, L 2022, 'Molecular characterization of colorectal cancer related peritoneal metastatic disease', Nature Communications, vol. 13, no. 1, 4443. https://doi.org/10.1038/s41467-022-32198-z

TY - JOUR

T1 - Molecular characterization of colorectal cancer related peritoneal metastatic disease

AU - Lenos, Kristiaan J

AU - Bach, Sander

AU - Ferreira Moreno, Leandro

AU - Ten Hoorn, Sanne

AU - Sluiter, Nina R

AU - Bootsma, Sanne

AU - Vieira Braga, Felipe A

AU - Nijman, Lisanne E

AU - van den Bosch, Tom

AU - Miedema, Daniel M

AU - van Dijk, Erik

AU - Ylstra, Bauke

AU - Kulicke, Ruth

AU - Davis, Fred P

AU - Stransky, Nicolas

AU - Smolen, Gromoslaw A

AU - Coebergh van den Braak, Robert R J

AU - IJzermans, Jan N M

AU - Martens, John W M

AU - Hallam, Sally

AU - Beggs, Andrew D

AU - Kops, Geert J P L

AU - Lansu, Nico

AU - Bastiaenen, Vivian P

AU - Klaver, Charlotte E L

AU - Lecca, Maria C

AU - El Makrini, Khalid

AU - Elbers, Clara C

AU - Dings, Mark P G

AU - van Noesel, Carel J M

AU - Kranenburg, Onno

AU - Medema, Jan Paul

AU - Koster, Jan

AU - Koens, Lianne

AU - Punt, Cornelis J A

AU - Tanis, Pieter J

AU - de Hingh, Ignace H

AU - Bijlsma, Maarten F

AU - Tuynman, Jurriaan B

AU - Vermeulen, Louis

PY - 2022/8/4

Y1 - 2022/8/4

N2 - 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.

AB - 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.

KW - Colorectal Neoplasms/pathology

KW - Humans

KW - Neoplasms, Second Primary

KW - Peritoneal Neoplasms/genetics

KW - Peritoneum/metabolism

KW - Quality of Life

KW - ERM PROTEINS

KW - INSTABILITY

KW - PROGNOSIS

KW - COLON

KW - PREVALENCE

KW - IDENTIFICATION

KW - FAMILY

KW - BRAF MUTATION

KW - CARCINOMATOSIS

KW - KRAS

U2 - 10.1038/s41467-022-32198-z

DO - 10.1038/s41467-022-32198-z

M3 - Article

C2 - 35927254

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4443

ER -

Molecular characterization of colorectal cancer related peritoneal metastatic disease

Abstract

Keywords

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