We use factor induced reprogramming of differentiated cells into self-renewing iPS cells as a model for initiation of cancer. Many of the reprogramming factors such as OCT4, KLF4, SOX2, MYC and LIN28 are known oncogenes and we are interested in determining how their overexpression compromises genome integrity. We have recently shown using high throughput sequencing and copy number analysis that iPS cells incur both nonsynonymous coding mutations (Ji et al, under review at Cell Stem Cell) and copy number variation (Hussein et al, Nature 2011). Current projects in the lab investigate the mechanisms via which reprogramming factors compromise genome integrity of iPS cells and seek to identify factors and conditions that minimize mutations in iPS cells.