ヒトの癌細胞系における突然変異の特徴は,エピソード的APOBEC変異を明らかにする

Mia Petljak¹, Ludmil B Alexandrov², Jonathan S Brammeld¹

¹Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK.

Cell

|March 9, 2019

まとめ

がん細胞系は進行中の変異パターンを示しています DNAの修復と複製のシグネチャは安定している一方で APOBECの編集は変動する爆発的な活動を示し癌ゲノム進化の洞察を提供します

科学分野:

ゲノミクス
癌生物学
分子生物学

背景:

癌ゲノムを理解する鍵となるものです癌ゲノムを理解する鍵となるものです
以前の研究では,がん細胞系と異種移植で共通する突然変異のサインを特定しました.

研究の目的:

癌細胞系における突然変異のシグネチャー生成の進行パターンを調査する.
外部変異因子や内生的なプロセスが継続的なシグネチャー形成を誘発するかどうかを判断する.

主な方法:

ヒトの癌細胞系を長期にわたって培養する
変異パターンを分析するために培養細胞のDNA配列解析
in vitroで生成されたシグネチャと,既知の in vivoシグネチャを比較する.

主要な成果:

タバコの煙や紫外線などの外部からの曝露によるシグネチャーは in vitro で生成されませんでした.
DNAの修復と複製に関連するシグネチャーが一貫して生成されました.
APOBECサイチジンデアミナーゼのシグネチャーは,エピソード的な勃発で,大きな時間的な変動を示した.

結論:

がん細胞系は進行中の内生的な変異プロセスをモデル化することができます.
APOBECの活動は,レトロトランスポゾンを含む可能性のある不明な開始因子による爆発によって特徴付けられています.
これらの細胞系はヒトの癌の変異過程を研究するための貴重な実験モデルとして機能します.

キーワード:

APOBECデアミナーゼがん細胞系エピソード性突然変異変異シグネチャー異種移植

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