Association between mutant IDHs and tumorigenesis in gliomas

研究成果: Review article

抄録

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.

元の言語English
ページ(範囲)194-198
ページ数5
ジャーナルMedical Molecular Morphology
51
発行部数4
DOI
出版物ステータスPublished - 01-12-2018

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Glioma
Carcinogenesis
Telomerase
Telomere
Astrocytes
Histones
Telomere Homeostasis
DNA Methylation
Methylation
Lysine
Genome
Mutation
Clinical Studies

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology

これを引用

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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.",
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Association between mutant IDHs and tumorigenesis in gliomas. / Ohba, Shigeo; Hirose, Yuichi.

:: Medical Molecular Morphology, 巻 51, 番号 4, 01.12.2018, p. 194-198.

研究成果: Review article

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