Degree and site of chromosomal instability define its oncogenic potential

Wilma H. M. Hoevenaar, Aniek Janssen, Ajit I. Quirindongo, Huiying Ma, Sjoerd J. Klaasen, Antoinette Teixeira, Bastiaan Gerwen, Nico Lansu, Folkert H. M. Morsink, G. Johan A. Offerhaus, René H. Medema, Geert J. P. L. Kops () and Nannette Jelluma ()
Additional contact information
Wilma H. M. Hoevenaar: Hubrecht Institute-KNAW and University Medical Center Utrecht
Aniek Janssen: University Medical Center Utrecht
Ajit I. Quirindongo: Hubrecht Institute-KNAW and University Medical Center Utrecht
Huiying Ma: University Medical Center Utrecht
Sjoerd J. Klaasen: Hubrecht Institute-KNAW and University Medical Center Utrecht
Antoinette Teixeira: Hubrecht Institute-KNAW and University Medical Center Utrecht
Bastiaan Gerwen: Hubrecht Institute-KNAW and University Medical Center Utrecht
Nico Lansu: Hubrecht Institute-KNAW and University Medical Center Utrecht
Folkert H. M. Morsink: University Medical Center Utrecht
G. Johan A. Offerhaus: University Medical Center Utrecht
René H. Medema: Netherlands Cancer Institute, Oncode Institute
Geert J. P. L. Kops: Hubrecht Institute-KNAW and University Medical Center Utrecht
Nannette Jelluma: Hubrecht Institute-KNAW and University Medical Center Utrecht

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract Most human cancers are aneuploid, due to a chromosomal instability (CIN) phenotype. Despite being hallmarks of cancer, however, the roles of CIN and aneuploidy in tumor formation have not unequivocally emerged from animal studies and are thus still unclear. Using a conditional mouse model for diverse degrees of CIN, we find that a particular range is sufficient to drive very early onset spontaneous adenoma formation in the intestine. In mice predisposed to intestinal cancer (ApcMin/+), moderate CIN causes a remarkable increase in adenoma burden in the entire intestinal tract and especially in the distal colon, which resembles human disease. Strikingly, a higher level of CIN promotes adenoma formation in the distal colon even more than moderate CIN does, but has no effect in the small intestine. Our results thus show that CIN can be potently oncogenic, but that certain levels of CIN can have contrasting effects in distinct tissues.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15279-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15279-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-15279-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().