Neurological Surgery 脳神経外科48巻2号

2020年02月発行

総説

脳腫瘍のゲノム・エピゲノム解析—神経膠腫を中心に

著者： 武笠晃丈¹

所属機関： ¹熊本大学大学院生命科学研究部脳神経外科学講座

ページ範囲：P.103 - P.115

Ⅰ．はじめに—脳腫瘍におけるゲノム・エピゲノム研究の意義—
　がんを含む多くの腫瘍は，細胞の設計図であるDNAの異常により生じると考えられている．このDNAの異常はさまざまであり，染色体の一部が増幅・欠失したり，異常な融合をしたりするような規模の大きいものもあれば，DNAを構成するアデニン（A），チミン（T），シトシン（C），グアニン（G）のヌクレオチドの配列が変異などにより小さく変化したり，少し欠損したりするといったものもある．近年ではまた，この親から子へと受け継がれ得るDNAにより構成されるゲノムの異常に対し，後天的なゲノムの修飾により細胞ごとの運命決定や機能制御にかかわる，DNAやクロマチンの化学修飾を主としたエピゲノムの異常によっても，多くの腫瘍が生じることも知られるようになった．
　がんがゲノムの異常によるものであり，その解明が重要という点は，1986年の『Science』にて「がんに対する理解を深めるためには全ゲノムのシーケンス解析をすべきだ」と提言された，ノーベル生理学・医学賞受賞者レナート・ドゥルベッコ先生の有名な言葉からもわかるように，以前から共有された課題であった¹⁹⁾．それが，その後の解析技術の驚くべき進歩によって次々と新たなゲノム・エピゲノム異常が明らかとなり，前世紀には想像もしなかったレベルで，脳腫瘍を含むがんゲノム異常の病態が解明されつつある．腫瘍の診断・治療には，その発生の元となったゲノム・エピゲノム異常の理解が極めて重要であることは疑うべくもないことであり，本稿においては，これまでに明らかとなってきた種々の脳腫瘍のゲノム・エピゲノム異常につき，神経膠腫の最近の知見を中心に概説するとともに，今後解決すべき問題点や研究の方向性などを考察したい．

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