Cancer arises primarily through accumulation of genetic mutations. Although derivation of induced pluripotent stem cell (iPSC) does not require changes in genomic sequence, somatic cells acquire the unlimited growth potential during reprogramming, a characteristic shared with cancer cells. Indeed, our previous studies have revealed an impact of reprogramming-related epigenetic regulation on development of various cancers. We showed that transient expression of reprogramming factors in vivo results in development of cancer that resembles human pediatric cancers. Indeed, the partial reprogramming-induced kidney tumors exhibited similar characteristics with human Wilms‘ tumors, which include aberrant DNA hypermethylation at H19 imprinting control region (ICR). Notably, the tumor cells gave rise to iPSCs that could contribute to chimeric mice. Moreover, the chimeric mice were born and grew normally without an obvious phenotype. Here we show that in vivo reprogramming with higher levels of reprogramming factors causes development of cancers that exhibit shared characteristics with human germ cell tumors. Like germ cell tumors, propagated tumor cells could differentiate into trophoblasts. In sharp contrast to H19 ICR hypermethylation in Wilms‘ tumor-like cancers, these tumors display a global reduction in ICR methylation, which is an unique epigenetic aberration in human germ cell tumors. Remarkably, germ cell tumor-like cancer cells give rise to iPSCs with the expanded differentiation potential to trophoblasts, which could contribute to extra-embryonic cells in the placenta as well as non-neoplastic somatic cells in vivo. Collectively, these findings underscore the central role of epigenetic regulation, but not genetic transformation, in the development of particular types of cancer.