ヒトの食道にコロニーを植える

Iñigo Martincorena¹, Joanna C Fowler², Agnieszka Wabik²

¹Wellcome Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK. im3@sanger.ac.uk pj3@sanger.ac.uk.

Science (New York, N.Y.)

|October 20, 2018

まとめ

体内の変異は年齢とともに固有のプロセスによって正常な食道細胞に蓄積されます NOTCH1やTP53のような癌に関連した変異を持つクローンは大きく拡大し老化や癌の発生に影響します

科学分野:

遺伝学
癌生物学
老化に関する研究

背景:

正常な組織における体内の変異の蓄積を理解することは,老化と癌の研究にとって極めて重要です.
過去の研究では,健康な成人の組織におけるクローン拡張の範囲と要因を完全に解明できませんでした.

研究の目的:

正常なヒト食道上皮質の変異性クローンのマッピングと特徴付け
年齢,体内の変異,クローン拡大の関係を調査する.
正常な食道上皮質でポジティブな選択下で特定の遺伝子を特定する.

主な方法:

幅広い年齢層 (20~75歳) の9人のドナーの正常な食道上皮のゲノム配列解析
体内の突然変異の蓄積とクローン拡大パターンの分析.
陽性選択による突然変異の遺伝子の特定

主要な成果:

ソマティック変異は,主に内在的な変異プロセスにより,年齢とともに蓄積されます.
14の癌遺伝子に変異があるクローンでは,有意な陽性選択が観察されました.
高齢のドナーでは,がん関連変異 (NOTCH1,TP53) を有するクローンは,上皮の大部分を占めていた.
NOTCH1変異の流行は,正常な食道における食道がんの流行を上回った.

結論:

正常な食道上皮は,年齢と内在的な変異過程の影響で,癌に関連した変異を持つクローンを拡張します.
正常組織におけるNOTCH1変異の高い流行は,がんの発生と老化における複雑な役割を示唆している.
これらの発見は,がんの病原化と老化における初期変異の再評価を必要とします.

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