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Tumours are a collection of genetically distinct cellular lineages related that must compete against each other and the external environment. Many cell lineages die out, while those with phenotypes that are advantageous expand. A major clinical consequence of this evolutionary process is the emergence of drug resistant tumour cells.
We have established an in vitro model system in which we can induce the human well-differentiated liposarcoma (WDLPS) cell line 778 to acquire resistance to the MDM2 inhibitor Nutlin-3a. I will detail we have applied bioinformatics and evolutionary principles to reconstruct major evolutionary events that occurred as this line acquired drug resistance. Integration of SNP array and exome sequencing data from different time points during the evolution of Nutlin resistance allow us to infer the relative order of genetic changes and how the rate of evolution fluctuated during the course of the experiment.