TY - JOUR
T1 - Degree and site of chromosomal instability define its oncogenic potential
AU - Hoevenaar, Wilma H M
AU - Janssen, Aniek
AU - Quirindongo, Ajit I
AU - Ma, Huiying
AU - Klaasen, Sjoerd J
AU - Teixeira, Antoinette
AU - van Gerwen, Bastiaan
AU - Lansu, Nico
AU - Morsink, Folkert H M
AU - Offerhaus, G Johan A
AU - Medema, René H
AU - Kops, Geert J P L
AU - Jelluma, Nannette
PY - 2020/3/20
Y1 - 2020/3/20
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-020-15279-9
DO - 10.1038/s41467-020-15279-9
M3 - Article
C2 - 32198375
SN - 2041-1723
VL - 11
SP - 1501
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -