研究遗传或生殖细胞基因组已经发现了具有大效应的罕见突变和与癌症风险相关的效应规模较小的常见多态性，这些研究在癌症的发病机理和发展方面有了重大启示，特别是在癌症预防方面具有特殊意义。同时，肿瘤体细胞基因组研究对于确定癌症发展的关键因素和显著地影响现代癌症治疗。虽然这些研究迄今为止基本上是分开进行的，但整合研究，即在同一患者中映射生殖和体细胞基因组的研究，有潜力为癌症生物学提供新颖而全面的见解。在《癌症研究》杂志上，刘和他的同事报告了超过12,000位癌症患者和11种癌症类型的整合性生殖和体细胞分析结果，发现一些关联性，其中规定了一些调节邻近基因在正常组织中表达的遗传变异与同一基因的肿瘤突变或全基因组体细胞特征（如肿瘤突变负担）有关。尽管需要进行大量的后续工作，但该研究是对目前证据不断涌现的重要贡献，证实了生殖细胞在塑造肿瘤基因组中具有重要作用。详细内容请参见刘等人的相关文章，第1191页. © 2023美国癌症研究协会。

Studies of the inherited or germline genome have identified rare mutations with large effects and common polymorphisms of more modest effect sizes that are associated with cancer risk. This research has substantially illuminated the etiology and development of cancer, with particular relevance to cancer prevention. In parallel, studies of the somatic or tumor genome have been instrumental in identifying the key drivers of cancer progression, significantly informing modern cancer therapy. While these studies have thus far largely been performed separately, integrative studies where the germline and somatic genomes are mapped in the same individuals have the potential to yield novel and holistic insights into cancer biology. In this issue of Cancer Research, Liu and colleagues report the results of integrative germline-somatic analyses in over 12,000 patients with cancer and 11 cancer types, identifying several associations where inherited variants that regulate the expression of a nearby gene in normal tissues are associated with tumor mutations in the same gene or with genome-wide somatic traits such as the tumor mutational burden. Although considerable follow-up work is required, the study is an important contribution to an emerging body of evidence that is demonstrating that the germline has a vital role in shaping the tumor genome. See related article by Liu et al., p. 1191.©2023 American Association for Cancer Research.