Characterisation_of_checkpoint_deficient_tumours_to_identify_alterations_that_allow_survival_of_chromosomal_instable_cells-sc-2011-04-05T16:03:54Z-1791
Characterisation_of_checkpoint_deficient_tumours_to_identify_alterations_that_allow_survival_of_chromosomal_instable_cells
We want to compare the mutations in 20 different mouse tumors: 4 Mps1f/f; p53f/+; 4 Mps1f/f; p53f/f; 4 Mad2f/f; p53f/f and 4 p53 f/f tumors. As the tumors in the first 3 groups show significantly more  chromosomal instability as tumors in the p53f/f control group, we want to compare the mutation load in these 4 groups which hopefully will provide more insight into the processes that allow for chromosomal instable tumors to survive.
Aneuploidy and chromsomal nistability are hallmarks of tumors. We have generated mouse models in which we can induce chromosomal instability by abrogating the sopindle checkpoint in a tissue of choice. In  the T-cell compartment chromosomal instability dramatically accelerates p53-driven lymphomagenesis. We have generated a large cohort of chromosomal instable tumors. Whereas thse tumors are highly aneuploid and show whole chromosome  abnormalities as expected  as evidenced by aCGH, we also find focal amplifications and deletions, suggesting that whole chromosome   instability coincided with structural chromosomal instability. As whole chromosomal instability is highly lethal to cells in tissue culture, we want top indentify genomic alterations that can explain the surcvival of these tumor cells in vivo.