Institut de Cancérologie de Lorraine, Service de Biopathologie, Vandœuvre-lès-Nancy, France.
Inserm U954, Faculté de Médecine de Nancy, Université de Lorraine, Vandœuvre-lès-Nancy, France; Service d'Hématologie Biologique, Pôle Laboratoires, Centre Hospitalier Régional et Universitaire de Nancy, Vandœuvre-lès-Nancy, France.
Arch Med Res. 2018 Jul;49(5):297-305. doi: 10.1016/j.arcmed.2018.10.007. Epub 2018 Nov 7.
Genetic alterations in tumors, as predictor of response to targeted-therapies or as prognostic markers, are clinically relevant to determine adequate therapeutic management. Tumor biopsy is currently the golden standard for somatic alterations assessment, but this approach is invasive and does not consider tumor heterogeneity. In various body fluids like plasma, somatic mutations have been identified. Circulating tumor DNA (ctDNA) holds promises in tumor burden monitoring or malignancies early detection. Since allele frequencies of circulating somatic mutations are low, highly sensitive novel assays have been developed to allow the investigation of the tumor genome, leading to the emergence of the "liquid biopsy" concept. Despite these technological advances, other assays for identifying intratumor and intermetastases heterogeneity need to be developed. Before being applied to clinic, ctDNA analyses need to be harmonized and validated with well-powered, well-designed studies. One of the primary prerequisite to incorporation of ctDNA analysis in the follow-up strategy of malignancies is the checking of the concordance with golden standard detection methods, imaging, circulating proteins and biopsy. This review focuses on the clinical interest of ctDNA in solid tumors and hematological malignancies.
肿瘤中的遗传改变可作为预测对靶向治疗的反应或作为预后标志物，与确定适当的治疗管理密切相关。肿瘤活检目前是评估体细胞改变的金标准，但这种方法具有侵入性，并且不能考虑肿瘤异质性。在血浆等各种体液中已经鉴定出了体细胞突变。循环肿瘤 DNA（ctDNA）在肿瘤负担监测或恶性肿瘤早期检测方面具有很大的应用前景。由于循环体突变等位基因频率较低，因此已经开发了高度敏感的新型检测方法来研究肿瘤基因组，从而产生了“液体活检”的概念。尽管有这些技术进步，但仍需要开发其他用于鉴定肿瘤内和转移灶异质性的检测方法。在将 ctDNA 分析应用于临床之前，需要对其进行协调并使用强有力的、精心设计的研究进行验证。将 ctDNA 分析纳入恶性肿瘤随访策略的主要前提之一是检查与金标准检测方法、影像学、循环蛋白和活检的一致性。本文综述了 ctDNA 在实体瘤和血液恶性肿瘤中的临床应用。
