@article{69745ad1c3674a9c84823860973d9e35,
title = "Modeling familial cancer with induced pluripotent stem cells",
abstract = "Summary In vitro modeling of human disease has recently become feasible with induced pluripotent stem cell (iPSC) technology. Here, we established patient-derived iPSCs from a Li-Fraumeni syndrome (LFS) family and investigated the role of mutant p53 in the development of osteosarcoma (OS). LFS iPSC-derived osteoblasts (OBs) recapitulated OS features including defective osteoblastic differentiation as well as tumorigenic ability. Systematic analyses revealed that the expression of genes enriched in LFS-derived OBs strongly correlated with decreased time to tumor recurrence and poor patient survival. Furthermore, LFS OBs exhibited impaired upregulation of the imprinted gene H19 during osteogenesis. Restoration of H19 expression in LFS OBs facilitated osteoblastic differentiation and repressed tumorigenic potential. By integrating human imprinted gene network (IGN) into functional genomic analyses, we found that H19 mediates suppression of LFS-associated OS through the IGN component DECORIN (DCN). In summary, these findings demonstrate the feasibility of studying inherited human cancer syndromes with iPSCs.",
author = "Lee, {Dung Fang} and Jie Su and Kim, {Huen Suk} and Betty Chang and Dmitri Papatsenko and Ruiying Zhao and Ye Yuan and Julian Gingold and Weiya Xia and Henia Darr and Razmik Mirzayans and Hung, {Mien Chie} and Christoph Schaniel and Lemischka, {Ihor R.}",
note = "Funding Information: We thank P. Yang, X. Wei, C.-K. Chou, C.F. Pereira, Y. Liu, and X. Niu, for experimental assistance. We also thank E. Lopez-Rivera and M. Li for CAM assay assistance, the Mount Sinai Genomic Core Facility and Columbia Genome Center for mRNA-seq analysis, as well as Mount Sinai{\textquoteright}s Flow Cytometry Core for sorting MSCs. We gratefully acknowledge K.A. Moore, and A. Waghray for discussions. This research was funded by grants from the NIH (5R01GM078465), the Empire State Stem Cell Fund through New York State Department of Health (NYSTEM; C024176 and C024410) to I.R.L.; The University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund, The National Breast Cancer Foundation Inc., the Program for Stem Cell and Regenerative Medicine Frontier Research (NSC 102-2321-B-039-001 [Taiwan]) to M.-C.H.; the Canadian Breast Cancer Foundation-Prairies/NWT region to R.M.; and NIH Pathway to Independence Award (K99CA181496) to D.-F.L. B.C. is a trainee in NIDCR-Interdisciplinary Training in Systems and Developmental Biology and Birth Defects (T32HD075735). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = apr,
day = "9",
doi = "10.1016/j.cell.2015.02.045",
language = "English",
volume = "161",
pages = "240--254",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}