@article{509d529c039848ac8741b55c242e9832,
title = "Centrosome Amplification Is Sufficient to Promote Spontaneous Tumorigenesis in Mammals",
abstract = "Centrosome amplification is a common feature of human tumors, but whether this is a cause or a consequence of cancer remains unclear. Here, we test the consequence of centrosome amplification by creating mice in which centrosome number can be chronically increased in the absence of additional genetic defects. We show that increasing centrosome number elevated tumor initiation in a mouse model of intestinal neoplasia. Most importantly, we demonstrate that supernumerary centrosomes are sufficient to drive aneuploidy and the development of spontaneous tumors in multiple tissues. Tumors arising from centrosome amplification exhibit frequent mitotic errors and possess complex karyotypes, recapitulating a common feature of human cancer. Together, our data support a direct causal relationship among centrosome amplification, genomic instability, and tumor development.",
keywords = "Plk4, aneuploidy, centriole, centrosome amplification, genomic instability, mitosis, tumorigenesis",
author = "Levine, {Michelle S.} and Bjorn Bakker and Bram Boeckx and Julia Moyett and James Lu and Benjamin Vitre and Spierings, {Diana C.} and Lansdorp, {Peter M.} and Cleveland, {Don W.} and Diether Lambrechts and Floris Foijer and Holland, {Andrew J.}",
note = "Funding Information: We thank Dr. Randall Reed for comments on this manuscript. We thank Dr. Cory Brayton, DVM, for pathological analysis of all mouse tissues in this manuscript. This work was supported by a Pew-Stewart Scholar Award (118110, to A.J.H.), a Kimmel Scholar Award (117829, to A.J.H.), a Johns Hopkins School of Medicine Innovation Award (to A.J.H.), a P30 grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, P30DK09086) (to A.J.H.), an American Cancer Society Scholar Award (RSG-16-156-01-CCG) (to A.J.H.), a Dutch Cancer Society grant (2012-RUG-5549) (to F.F.), and research grants GM 114119 (to A.J.H.) and GM 29513 (to D.W.C.) from the NIH. We thank Nancy Halsema, Inge Kazemier, and Karina Hoekstra-Wakker for technical help with single-cell sequencing. Financial support for single-cell sequencing was provided in part by a European Research Council Advanced grant (ROOTS-Grant Agreement 294740) to P.M.L.",
year = "2017",
month = feb,
day = "6",
doi = "10.1016/j.devcel.2016.12.022",
language = "English (US)",
volume = "40",
pages = "313--322.e5",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "3",
}