Mutant IDH1 is required for IDH1 mutated tumor cell growth
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Genglin Jin1, Christopher J. Pirozzi1, Lee H. Chen1, Giselle Y. Lopez1, Christopher G. Duncan1, Jie Feng1, Ivan Spasojevic2, Darell D. Bigner1, Yiping He1, and Hai Yan1
1 The Preston Robert Tisch Brain Tumor Center, The Pediatric Brain Tumor Foundation Institute, and The Department of Pathology,
2 The Clinical Pharmacology Laboratory, Duke Cancer Institute and Department of Medicine/Oncology, Duke University Medical Center, Durham, North Carolina, USA
Hai Yan, email:
Keywords: IDH1, cell survival
Received: July 27, 2012, Accepted: August 04, 2012, Published: August 09, 2012
Frequent somatic hotspot mutations in isocitrate dehydrogenase 1 (IDH1) have been identified in gliomas, acute myeloid leukemias, chondrosarcomas, and other cancers, providing a likely avenue for targeted cancer therapy. However, whether mutant IDH1 protein is required for maintaining IDH1 mutated tumor cell growth remains unknown. Here, using a genetically engineered inducible system, we report that selective suppression of endogenous mutant IDH1 expression in HT1080, a fibrosarcoma cell line with a native IDH1R132C heterozygous mutation, significantly inhibits cell proliferation and decreases clonogenic potential. Our findings offer insights into changes that may contribute to the inhibition of cell proliferation and offer a strong preclinical rationale for utilizing mutant IDH1 as a valid therapeutic target.
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