Altered A-to-I RNA editing has been widely observed in many human cancers and some editing sites are associated with drug sensitivity, implicating its therapeutic potential. Increasing evidence has demonstrated that a quantitative trait loci mapping approach is effective to understanding the genetic basis of RNA editing. We systematically performed RNA editing quantitative trait loci (edQTL) analysis in 33 human cancer types for >10 000 cancer samples and identified 320 029 edQTLs. We also identified 1688 ed-QTLs associated with patient overall survival and 4672 ed-QTLs associated with GWAS risk loci. Furthermore, we demonstrated the associations between RNA editing and >1000 anti-cancer drug response with ∼3.5 million significant associations. We developed GPEdit (https://hanlab.uth.edu/GPEdit/) to facilitate a global map of the genetic and pharmacogenomic landscape of RNA editing. GPEdit is a user-friendly and comprehensive database that provides an opportunity for a better understanding of the genetic impact and the effects on drug response of RNA editing in cancers.

中文翻译：

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GPEdit：癌症中 A-to-I RNA 编辑的遗传和药物基因组学格局

在许多人类癌症中广泛观察到改变的 A-to-I RNA 编辑，并且一些编辑位点与药物敏感性相关，暗示其治疗潜力。越来越多的证据表明，数量性状位点作图方法对于理解 RNA 编辑的遗传基础是有效的。我们系统地对 33 种人类癌症类型进行了大于 10 000 个癌症样本的 RNA 编辑数量性状基因座 (edQTL) 分析，并鉴定了 320 029 个 edQTL。我们还确定了与患者总生存期相关的 1688 个 ed-QTL 和与 GWAS 风险位点相关的 4672 个 ed-QTL。此外，我们证明了 RNA 编辑与大于 1000 种抗癌药物反应之间的关联，其中约 350 万个显着关联。我们开发了 GPEdit (https://hanlab.uth. edu/GPEdit/) 以促进 RNA 编辑的遗传和药物基因组学格局的全球地图。GPEdit 是一个用户友好且全面的数据库，它为更好地了解癌症中 RNA 编辑对遗传影响和药物反应的影响提供了机会。