Center for Noninvasive Diagnostics, Translational Genomics Research Institute, Phoenix, AZ, USA.
Center for Noninvasive Diagnostics, Translational Genomics Research Institute, Phoenix, AZ, USA; Mayo Clinic Center for Individualized Medicine, Scottsdale, AZ, USA.
Pharmacol Ther. 2017 Jun;174:22-26. doi: 10.1016/j.pharmthera.2017.02.003. Epub 2017 Feb 3.
Circulating tumor DNA analysis has emerged as a potential noninvasive alternative to tissue biopsies for tumor genotyping in patients with metastatic cancer. This is particularly attractive in cases where tissue biopsies are contraindicated or repeat genotyping after progression on treatment is required. However, tissue and plasma analysis results are not always concordant and clinical interpretation of discordant results is not completely understood. Discordant results could arise due to analytical limits of assays used for tumor and plasma DNA analysis or due to low overall contribution of tumor-specific DNA in plasma. Once these factors are ruled out, tissue-plasma concordance and quantitative levels of somatic mutations in plasma can capture tumor heterogeneity. During longitudinal follow-up of patients, this feature can be leveraged to track subclonal evolution and to guide combination or sequential adaptive treatment. Here, we summarize recent results evaluating the opportunities and limitations of circulating tumor DNA analysis in the context of tumor heterogeneity and subclonal evolution in patients with advanced cancers.
循环肿瘤 DNA 分析已成为一种潜在的非侵入性方法，可替代转移性癌症患者的肿瘤基因分型组织活检。在组织活检禁忌或需要在治疗进展后重复进行基因分型的情况下，这种方法特别有吸引力。然而，组织和血浆分析结果并不总是一致的，对于不一致结果的临床解释也不完全清楚。不一致的结果可能是由于用于肿瘤和血浆 DNA 分析的检测分析的局限性，或者由于血浆中肿瘤特异性 DNA 的总体贡献较低所致。一旦排除了这些因素，组织-血浆一致性以及血浆中体细胞突变的定量水平就可以捕获肿瘤异质性。在对患者进行纵向随访期间，可以利用这一特征来跟踪亚克隆进化，并指导联合或序贯适应性治疗。在这里，我们总结了最近的研究结果，评估了循环肿瘤 DNA 分析在晚期癌症患者肿瘤异质性和亚克隆进化背景下的机会和局限性。
