Interrogating the tumor genome in its entirety by whole-genome sequencing (WGS) offers an unprecedented insight into the biology and pathogenesis of cancer, with potential impact on diagnostics, prognostication and therapy selection. WGS is able to detect sequence as well as structural variants and thereby combines central domains of cytogenetics and molecular genetics. Given the potential of WGS in directing targeted therapeutics and clinical decision-making, we envision a gradual transition of the method from research to clinical routine. This review is one out of three within this issue aimed at facilitating this effort, by discussing in-depth analytical validation, clinical interpretation and clinical utility of WGS. The review highlights the requirements for implementing, validating and maintaining a clinical WGS pipeline to obtain high-quality patient-specific data in accordance with the local regulatory landscape. Every step of the WGS pipeline, which includes DNA extraction, library preparation, sequencing, bioinformatics analysis, and data storage, is considered with respect to its logistics, necessities, potential pitfalls, and the required quality management. WGS is likely to drive clinical diagnostics and patient care forward, if requirements and challenges of the technique are recognized and met.

通过全基因组测序 (WGS) 对整个肿瘤基因组进行询问，为癌症的生物学和发病机制提供了前所未有的洞察力，对诊断、预后和治疗选择具有潜在影响。WGS 能够检测序列和结构变异，从而结合细胞遗传学和分子遗传学的中心域。鉴于 WGS 在指导靶向治疗和临床决策方面的潜力，我们设想该方法从研究逐渐过渡到临床常规。这篇综述是本期杂志中的三分之一，旨在通过深入讨论 WGS 的分析验证、临床解释和临床效用来促进这项工作。审查强调了实施的要求，验证和维护临床 WGS 管道，以根据当地监管环境获得高质量的患者特定数据。WGS 管道的每一步，包括 DNA 提取、文库制备、测序、生物信息学分析和数据存储，都需要考虑其物流、必要性、潜在缺陷和所需的质量管理。如果认识到并满足该技术的要求和挑战，WGS 可能会推动临床诊断和患者护理向前发展。以及所需的质量管理。如果认识到并满足该技术的要求和挑战，WGS 可能会推动临床诊断和患者护理向前发展。以及所需的质量管理。如果认识到并满足该技术的要求和挑战，WGS 可能会推动临床诊断和患者护理向前发展。