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Deletion of the MAD2L1 spindle assembly checkpoint gene is tolerated in mouse models of acute T-cell lymphoma and hepatocellular carcinoma.

Floris Foijer | Lee A Albacker | Bjorn Bakker | Diana C Spierings | Ying Yue | Stephanie Z Xie | Stephanie Davis | Annegret Lutum-Jehle | Darin Takemoto | Brian Hare | Brinley Furey | Roderick T Bronson | Peter M Lansdorp | Allan Bradley | Peter K Sorger
eLife | 2017

Chromosome instability (CIN) is deleterious to normal cells because of the burden of aneuploidy. However, most human solid tumors have an abnormal karyotype implying that gain and loss of chromosomes by cancer cells confers a selective advantage. CIN can be induced in the mouse by inactivating the spindle assembly checkpoint. This is lethal in the germline but we show here that adult T cells and hepatocytes can survive conditional inactivation of the Mad2l1 SAC gene and resulting CIN. This causes rapid onset of acute lymphoblastic leukemia (T-ALL) and progressive development of hepatocellular carcinoma (HCC), both lethal diseases. The resulting DNA copy number variation and patterns of chromosome loss and gain are tumor-type specific, suggesting differential selective pressures on the two tumor cell types.

Pubmed ID: 28318489

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P01 CA139980
  • Agency: NCI NIH HHS, United States
    Id: R01 CA084179

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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