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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.
Type
Journal articleSubject
Cell Line, TumorHumans
Fibrosarcoma
Isocitrate Dehydrogenase
RNA, Small Interfering
Cell Proliferation
RNA Interference
Mutation
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https://hdl.handle.net/10161/17850Published Version (Please cite this version)
10.18632/oncotarget.577Publication Info
(2012). Mutant IDH1 is required for IDH1 mutated tumor cell growth. Oncotarget, 3(8). pp. 774-782. 10.18632/oncotarget.577. Retrieved from https://hdl.handle.net/10161/17850.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Darell Doty Bigner
E. L. and Lucille F. Jones Cancer Distinguished Research Professor, in the School
of Medicine
The Causes, Mechanisms of Transformation and Altered Growth Control and New Therapy
for Primary and Metastatic Tumors of the Central Nervous System (CNS). There are
over 16,000 deaths in the United States each year from primary brain tumors such as
malignant gliomas and medulloblastomas, and metastatic tumors to the CNS and its covering
from systemic tumors such as carcinoma of the lung, breast, colon, and melanoma. An
estimated 80,000 cases of primary brain tumors were expected to
Yiping He
Associate Professor in Pathology
Giselle Yvette López
Assistant Professor in Pathology
I am a physician scientist with a clinical focus on neuropathology, and a research
interest in brain tumors. Originally from Maryland, I completed my undergraduate training
at the University of Maryland, completing degrees in Physiology and Neurobiology as
well as Spanish Language and Literature. I subsequently came to Duke for my MD and
PhD, and discovered a passion for brain tumor research, and quickly realized that
this was my life's calling. Clinically, I specialize in neuropathology. While
Christopher Pirozzi
Assistant Professor in Pathology
Dr. Pirozzi's work thus far has been dedicated to studying brain tumors, particularly
gliomas. During his research career, he has focused on identifying the common mutations
present in gliomas and how these different mutations correlate with diagnoses and
prognoses. To this end, Christopher was involved in several publications that identified
and stratified brain tumor patients based on their mutation spectrum. For example,
mutations in ATRX, CIC, FUBP1, and IDH1 can be used to distinguish pa
Ivan Spasojevic
Associate Professor in Medicine
Hai Yan
Adjunct Professor of Pathology
Our research activities center on the molecular genetics and biology of cancer with
a focus on the identification, characterization, and therapeutic targeting of driver
mutations involved in the genesis and progression of brain cancers. Gliomas are the
most common type of primary brain tumor. Through genomic studies, we have identified
mutations in IDH1 and IDH2 in 70% of progressive malignant gliomas. These are somatic
missense mutations that alter a conserved arginine residue and gain a
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