Association between mutant IDHs and tumorigenesis in gliomas

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Abstract

To become immortalized, cells need to maintain the telomere length via the activation of telomerase or alternative lengthening of telomere. Mutations in IDH1/2 are strongly associated with the early stage of gliomagenesis. Previous work has shown that the accumulation of 2-HG, which is induced by mutant IDH1/2, inhibits α-KG-dependent deoxygenase and leads to genome-wide histone and DNA methylation alterations. These alterations are believed to contribute to tumorigenesis. H-Ras can transform human astrocytes with the inactivation of p53/pRb and expression of hTERT; however, mutant IDH1 can also transform cells. Moreover, mutant IDH1 can drive the immortalization and transformation of p53-/pRb-deficient astrocytes by reactivating telomerase and stabilizing telomeres in combination with increased histone lysine methylation and c-Myc/Max binding at the TERT promoter. It remains unclear whether mutant IDH1/2 acts only as the initial driver of gliomagenesis or it maintains transformed cells. Clinical studies are being performed to assess the use of mutant IDH1/2 inhibitors for treating gliomas.

Keywords

Glioma Gliomagenesis Immortalization Mutant IDH Telomere TERT Transformation 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© The Japanese Society for Clinical Molecular Morphology 2018

Authors and Affiliations

  1. 1.Department of NeurosurgeryFujita Health UniversityToyoakeJapan

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