Neurological Surgery 脳神経外科40巻4号

2012年04月発行

総説

IDH遺伝子異常と脳腫瘍に関して

著者： 園田順彦¹ 冨永悌二²

所属機関： ¹仙台医療センター脳神経外科 ²東北大学大学院医学系研究科神経外科学

ページ範囲：P.297 - P.306

Ⅰ．はじめに

　神経膠腫の発生に関与する遺伝子異常としては，古くはepidermal growth factor receptor（EGFR）遺伝子の増幅あるいは変異，p53遺伝子異常，p16遺伝子のホモ欠失，PTEN遺伝子の異常，染色体1番短腕，19番長腕の共欠失（1p19q codeletion）などが報告されている．これらの遺伝子異常の頻度は神経膠腫の組織型，悪性度と相関しており，これをもとに膠芽腫（glioblastoma）の発生モデルが提唱され，今日に至っている（Fig. 1）．近年，欧米のグループによるgenome wide mutational analysisは多数例の膠芽腫DNAを網羅的にスクリーニングすることで，未知の膠芽腫発生に関与する遺伝子を発見しようという試みである．本プロジェクトにより多くの新しい知見がもたらされたが，その中で最も重要な発見の1つにイソクエン酸デヒドロゲナーゼ遺伝子（isocitrate dehydrogenase（IDH）遺伝子）の変異が挙げられる．この遺伝子異常は，膠芽腫の中で特に続発性膠芽腫（secondary glioblastoma）において高頻度に認められた²³⁾．本稿ではIDH遺伝子変異による機能異常，神経膠腫発生に関わるIDH遺伝子異常の役割を中心に最新の知見を紹介する．

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