Moss Esther L, Gorsia Diviya N, Collins Anna, Sandhu Pavandeep, Foreman Nalini, Gore Anupama, Wood Joey, Kent Christopher, Silcock Lee, Guttery David S
Leicester Cancer Research Centre, College of Life Sciences, University of Leicester, Leicester LE2 7LX, UK.
Department of Gynaecological Oncology, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester LE5 4PW, UK.
Cancers (Basel). 2020 Aug 10;12(8):2231. doi: 10.3390/cancers12082231.
Despite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients, using targeted next-generation sequencing (tNGS) and personalized ctDNA assays. Using tNGS, at least one somatic mutation at a variant allele frequency (VAF) > 20% was detected in 69% (9/13) of patient tumors. The four patients with no detectable tumor mutations at >20% VAF were whole exome sequenced, with all four harboring mutations in genes not analyzed by tNGS. Analysis of matched and longitudinal plasma DNA revealed earlier detection of EC recurrence and progression and dynamic kinetics of ctDNA levels reflecting treatment response. We also detected acquired high microsatellite instability (MSI-H) in ctDNA from one patient whose primary tumor was MSI stable. Our study suggests that ctDNA analysis could become a useful biomarker for early detection and monitoring of EC recurrence. However, further research is needed to confirm these findings and to explore their potential implications for patient management.
尽管全球子宫内膜癌（EC）的发病率不断上升，且复发患者的总体生存率较低，但在常规随访期间，尚无可靠的生物标志物用于检测和监测EC的复发及进展。循环肿瘤DNA（ctDNA）是一种监测癌症活性和对可能对治疗有反应的患者进行分层的敏感方法。作为一项试点研究，我们使用靶向新一代测序（tNGS）和个性化ctDNA检测方法，调查了ctDNA在13例患者中检测和监测EC复发及进展的效用。使用tNGS，在69%（9/13）的患者肿瘤中检测到至少一个变异等位基因频率（VAF）>20%的体细胞突变。对4例VAF>20%时未检测到肿瘤突变的患者进行了全外显子组测序，所有4例患者在未通过tNGS分析的基因中均存在突变。对匹配的纵向血浆DNA分析显示，能更早地检测到EC复发及进展，且ctDNA水平的动态变化反映了治疗反应。我们还在一名原发性肿瘤微卫星稳定的患者的ctDNA中检测到获得性高微卫星不稳定性（MSI-H）。我们的研究表明，ctDNA分析可能成为早期检测和监测EC复发的有用生物标志物。然而，需要进一步研究来证实这些发现，并探索其对患者管理的潜在意义。
