Mutant IDH Is Sufficient to Initiate Enchondromatosis in Mice
Mutant IDH is sufficient to initiate enchondromatosis in mice Makoto Hirataa, Masato Sasakib, Rob A. Cairnsb, Satoshi Inoueb, Vijitha Puviindranc, Wanda Y. Lib, Bryan E. Snowb, Lisa D. Jonesb, Qingxia Weia, Shingo Satoa, Yuning J. Tanga, Puviindran Nadesanc, Jason Rockela, Heather Whetstonea, Raymond Poona, Angela Wenga, Stefan Grossd, Kimberly Straleyd, Camelia Gliserd, Yingxia Xue, Jay Wunderf, Tak W. Makb,1,2, and Benjamin A. Almana,c,1,2 aProgram in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada, M5G 0A4; bThe Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada, M5G 2C1; cDepartment of Orthopedic Surgery, Duke University, Durham, NC 27710; dAgios Pharmaceuticals, Cambridge, MA 02139; eChempartner, Shanghai 201203, China; and fDepartment of Orthopedic Surgery, Mount Sinai Hospital, Toronto, ON, Canada, M5G 1X5 Contributed by Tak W. Mak, December 29, 2014 (sent for review November 11, 2014; reviewed by Navdeep S. Chandel, Nicholas C. Denko, and Jorge Moscat) Enchondromas are benign cartilage tumors and precursors to cartilage lesions to develop adjacent to the growth-plate cartilage malignant chondrosarcomas. Somatic mutations in the isocitrate in mice (8). dehydrogenase genes (IDH1 and IDH2) are present in the majority The majority of enchondromas and chondrosarcomas harbor of these tumor types. How these mutations cause enchondromas somatic isocitrate dehydrogenase 1 (IDH1)orIDH2 mutations is unclear. Here, we identified the spectrum of IDH mutations in (15–18). Mutations in IDH genes are common in several other human enchondromas and chondrosarcomas and studied their neoplasms, including glioma, glioblastoma, acute myeloid leu- effects in mice. A broad range of mutations was identified, includ- kemia, angioimmunoblatic T-cell lymphoma, and intrahepatic ing the previously unreported IDH1-R132Q mutation.
[Show full text]