title: Mutant IDH1 is required for IDH1 mutated tumor cell growth.
abstract: 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 IDH1(R132C) 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.
authors.affiliation: The Preston Robert Tisch Brain Tumor Center, The Pediatric Brain Tumor Foundation Institute, and The Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Genglin
authors.initials: G
authors.lastname: Jin
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pirozzi
authors.forename: Lee H
authors.initials: LH
authors.lastname: Chen
authors.forename: Giselle Y
authors.initials: GY
authors.lastname: Lopez
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Duncan
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojevic
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.forename: Yiping
authors.initials: Y
authors.lastname: He
authors.forename: Hai
authors.initials: H
authors.lastname: Yan
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005354:Fibrosarcoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D034741:RNA, Small Interfering; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human