In vitro evolution of chemotherapy resistance

The use of next generation sequencing (NGS) has revolutionized our understanding of tumor biology and the mechanisms associated with tumor development. However, the translation of cancer genomic data to therapeutic treatment remains challenging as evolution of tumor resistance to chemotherapeutic drugs is complicated by patient genetic heterogeneity and access to material for hypothesis-testing. Here we demonstrate that in vitro evolution and whole genome analysis (IVIEWGA) in the human, near-haploid chronic myelogenous leukemia (CML) cell line (HAP-1) can be used to identify genes associated with drug resistance in a controlled and reproducible manner. After evolving resistance to five different anticancer drugs (doxorubicin, gemcitabine, etoposide, topotecan, and paclitaxel), we performed whole genome sequencing (WGS) and whole exome sequencing (WES) on 28 independent resistant clones and their isogenic parents.