Molecular tests assist at various stages of cancer patient management, including providing diagnosis, predicting prognosis, identifying therapeutic targets, and determining hereditary cancer risk. The current testing paradigm involves germline testing in a subset of patients determined to be at high risk for having a hereditary cancer syndrome, and tumor-only sequencing for treatment decisions in advanced cancer patients. A major limitation of tumor-only sequencing is its inability to distinguish germline versus somatic mutations. Tumor-normal sequencing has emerged as a comprehensive analysis for both hereditary cancer predisposition and somatic profiling. Here, we review recent studies involving tumor-normal sequencing, discuss its benefits in clinical care, challenges for its implementation, and novel insights it has provided regarding tumor biology and germline contribution to cancer.

分子检测有助于癌症患者管理的各个阶段，包括提供诊断、预测预后、确定治疗靶点和确定遗传性癌症风险。当前的检测范式涉及对被确定为患有遗传性癌症综合征的高风险患者子集进行生殖系检测，以及对晚期癌症患者的治疗决策进行仅肿瘤测序。仅肿瘤测序的一个主要限制是它无法区分种系和体细胞突变。肿瘤正常测序已成为遗传性癌症易感性和体细胞分析的综合分析。在这里，我们回顾了最近涉及肿瘤正常测序的研究，讨论了其在临床护理中的益处，其实施面临的挑战，