p53遺伝子の変異は,さまざまなヒト腫瘍タイプで発生する

J M Nigro¹, S J Baker, A C Preisinger

¹Johns Hopkins Oncology Center, Baltimore, Maryland 21231.

Nature

|December 7, 1989

まとめ

p53遺伝子は,当初腫瘍遺伝子と考えられていたが,腫瘍抑制剤として機能している. p53遺伝子の変異は,様々なヒトがんで頻繁に観察され,しばしば染色体17の欠損とともに観察されます.

科学分野:

分子生物学は分子生物学である.
腫瘍学腫瘍学
遺伝学遺伝学とは

背景:

p53遺伝子の役割は,腫瘍遺伝子から腫瘍抑制剤へと進化した.
腫瘍抑制遺伝子は,削除と変異の両方によってしばしば不活性化されます.
染色体17pのアレル欠損は,大腸がんを含むヒト腫瘍において一般的です.

研究の目的:

染色体17pのアレル deletionsを持つ腫瘍におけるp53遺伝子変異の一般性を調査する.
保持されたp53アレルに欠損した腫瘍の変異があるかどうかを判断する.
p53遺伝子内の変異パターンを特定するために.

主な方法:

染色体17pの欠損を示す腫瘍におけるp53遺伝子状態 (アレル欠損と変異) の分析.
双方の親 17p アレルを保持した腫瘍におけるp53 アレルの検査.
p53遺伝子配列内の突然変異"ホットスポット"の特定.

主要な成果:

17pアレル欠損を有するほとんどの腫瘍には,p53点変異があり,アミノ酸の置換につながる.
p53変異は,アレル欠損がある場合とない場合の腫瘍で発生します.
p53変異は,保存された遺伝子領域に対応する4つの特定の"ホットスポット"に集中しています.

結論:

p53遺伝子変異は,多くの一般的なヒトの悪性腫瘍の病原性に関与しています.
変異によるp53腫瘍抑制遺伝子の不活性化は,がんの発症における重要な出来事です.
p53変異パターンの理解は,がんの病因学に関する洞察を提供することができます.

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