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Isocitrate dehydrogenase (IDH) mutations occur frequently in lower-grade gliomas, which result in genome-wide epigenetic alterations. The wild-type IDH1 is reported to participate in lipid biosynthesis and amino acid metabolism, but its role in tumorigenesis is still unclear. In this study, the expressions of IDH1 and podoplanin (Pdpn) were determined in IDH-mutated and IDH-wild-type gliomas, and their relationships in glioma were further analyzed. In addition, the regulation of wild-type IDH1 and mutant IDH1 on Pdpn expression was investigated by luciferase assays and promoter methylation analysis. Our study showed that Pdpn was almost undetectable in IDH-mutated glioma but strongly expressed in higher-grade IDH-wild-type glioma. Pdpn overexpression promoted the migration of glioma cells but had little effect on cell growth. Moreover, Pdpn expression was positively correlated with the increased wild-type IDH1 levels in IDH-wild-type glioma. Consistently, the wild-type IDH1 greatly promoted the transcription and expression of Pdpn, but the mutant IDH1 and D-2-hydroxyglutarate significantly suppressed Pdpn expression in glioma cells. Besides, our results revealed that the methylation of CpG islands in the Pdpn promoter was opposingly regulated by wild-type and mutant IDH1 in glioma. Collectively, our results indicated that wild-type and mutant IDH1 opposingly controlled the Pdpn expression in glioma by regulating its promoter methylation, which provides a basis for understanding the relationship between wild-type and mutant IDH1 in epigenetic regulation and tumorigenesis.
This article was published in the following journal.
Name: Translational oncology
Isocitrate dehydrogenase 1 (IDH1), which catalyzes the conversion of isocitrate to α-ketoglutarate, is one of key enzymes in the tricarboxylic acid cycle (TCA). Hotspot mutation at Arg in IDH1 that a...
Primary glioblastoma (GB) is the most aggressive type of brain tumors. While mutations in isocitrate dehydrogenase (IDH) genes are frequent in secondary GBs and correlate with a better prognosis, most...
Point mutations in human IDH1 can drive malignancies including lower grade gliomas and secondary glioblastomas, chondrosarcomas, and acute myeloid leukemias. These mutations, which usually affect resi...
The isocitrate dehydrogenase (IDH1/2) mutations are frequent genetic abnormalities in the majority of WHO grade II/III glioma and secondary GBM. IDH1-mutated (IDH1) glioma exhibits distinctive pattern...
Isocitrate dehydrogenase 1 mutations have been discovered in an array of hematologic malignancies and solid tumors. These mutations could cause the production of high levels of 2-hydroxyglutarate, whi...
This research study is studying a drug as a possible treatment for IDH1-mutant myeloid neoplasms. -The drug involved in this study is ivosidenib (AG-120)
The purpose of this study is to found out if the drug IDH305 is safe and effective in subjects with IDH1 mutant grade II or III glioma that has progressed after observation or radiation th...
This study is being done to see whether AG-120 is an effective and safe treatment for people with advanced/metastatic or recurrent chondrosarcoma that has IDH1 mutation.
1. To assess the incidence of IDH1 and IDH2 mutations in adult AML patients, and to explore their associations with the patients' clinical, cytogenetic, and molecular characteris...
patients with MDS (Myelodysplastic Syndrome) and mutated IDH1 patients will be treated with AG120 (IDH1 inhibitor)
A method of detecting gene mutation by mixing PCR-amplified mutant and wild-type DNA followed by denaturation and reannealing. The resultant products are resolved by gel electrophoresis, with single base substitutions detectable under optimal electrophoretic conditions and gel formulations. Large base pair mismatches may also be analyzed by using electron microscopy to visualize heteroduplex regions.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
Animals considered to be wild or feral or not adapted for domestic use. It does not include wild animals in zoos for which ANIMALS, ZOO is available.
Rats bearing mutant genes which are phenotypically expressed in the animals.
According to the American Brain Tumor Association, just over 24,000 patients will be diagnosed with a primary malignant brain tumour during 2012 in the US alone. Some 80% of primary malignant brain tumours are gliomas, a broad term which includes all tum...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...