Unknown,Transcriptomics,Genomics,Proteomics

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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 human cancer remains unclear. Here, we report the creation of a mouse model in which centrosome number can be persistently increased in the absence of additional genetic defects. We show that extra centrosomes increase tumor initiation in a mouse model of intestinal neoplasia. Most importantly, we demonstrate that supernumerary centrosomes are sufficient to drive development of spontaneous tumors in multiple tissues. Tumors with 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 between centrosome amplification, genomic instability and tumor development. The sequences in this dataset result from random whole-genome DNA sequencing of spontaneous T- cell lymphomas, B-cell lymphomas, squamous cell carcinomas and one sarcoma from doxycycline-treated Plk4 mice.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Mus musculus

SUBMITTER: Bram Boeckx 

PROVIDER: E-MTAB-5043 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications


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  ...[more]

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