癌症由种系和体细胞遗传变异共同推动。已经致力于表征癌症起始和发展过程中的基因变异。大多数关注点集中在蛋白编码基因以及与之相关的调控元件，如启动子和增强子的突变上。测序技术的发展以及基于计算机模拟和实验方法的应用，进一步促进了对非编码RNA中癌症易感变异和重要体细胞突变的探索，主要是针对长非编码RNA和微小RNA。包括基因关联研究在内的GWAS研究已经揭示了非编码RNA或miRNA基因和调控区域中的单核苷酸多态性和插入缺失突变。这些突变改变了RNA的二级结构、表达水平和靶标识别，从而使携带者易患癌症。对比癌组织和正常组织的全外显子/全基因组测序揭示了非编码RNA基因中的重要体细胞突变。在各种与肿瘤相关的非编码RNA中发现了突变热点和体细胞拷贝数改变。越来越多的关注和努力被用于研究基因组的非编码区域。癌症起始的复杂遗传网络正在被揭开。本文归类于：疾病与发育中的RNA > RNA与疾病。© 2023作者. Wiley Periodicals LLC出版的WIREs RNA.

Cancer is driven by both germline and somatic genetic changes. Efforts have been devoted to characterizing essential genetic variations in cancer initiation and development. Most attention has been given to mutations in protein-coding genes and associated regulatory elements such as promoters and enhancers. The development of sequencing technologies and in silico and experimental methods has allowed further exploration of cancer predisposition variants and important somatic mutations in noncoding RNAs, mainly for long noncoding RNAs and microRNAs. Association studies including GWAS have revealed hereditary variations including SNPs and indels in lncRNA or miRNA genes and regulatory regions. These mutations altered RNA secondary structures, expression levels, and target recognition and then conferred cancer predisposition to carriers. Whole-exome/genome sequencing comparing cancer and normal tissues has revealed important somatic mutations in noncoding RNA genes. Mutation hotspots and somatic copy number alterations have been identified in various tumor-associated noncoding RNAs. Increasing focus and effort have been devoted to studying the noncoding region of the genome. The complex genetic network of cancer initiation is being unveiled. This article is categorized under: RNA in Disease and Development > RNA in Disease.© 2023 The Authors. WIREs RNA published by Wiley Periodicals LLC.