TRACERx 100: metastatic samples

Whole exome sequencing of 10 metastatic biopsies from four TRACERx100 patients (see EGA dataset EGAS00001002247), collected either after relapse or death. The data from these samples are initially published with Abbosh, C. et al. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution. Nature http://dx.doi.org/10.1038/nature22364 (2017).

Abstract:
Earlier detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a patient-specific approach to ctDNA profiling in the first 100 lung TRACERx (TRAcking Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release in early-stage non-small cell lung cancer and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies.EGA study EGAS00001002415

本数据集针对4名TRACERx（TRAcking Cancer Evolution through therapy (Rx)）100研究的受试者的10份转移性活检样本开展全外显子组测序（Whole Exome Sequencing），相关样本采集于患者复发后或死亡阶段，对应数据集已收录于欧洲基因组学档案（EGA，European Genome-phenome Archive）数据集EGAS00001002247。该样本数据最初由Abbosh C.等人发表于《Nature》期刊的论文《Phylogenetic ctDNA分析揭示早期肺癌进化历程》（DOI: 10.1038/nature22364，2017年）。

摘要：
非小细胞肺癌患者接受原发肿瘤切除术后，若能更早检测到复发，并明确驱动转移灶形成的新兴亚克隆特征，或将为限制肿瘤复发提供全新治疗策略。目前，针对早期非小细胞肺癌患者的循环肿瘤DNA（ctDNA，circulating tumor DNA）开展无创肿瘤进化动态追踪的潜力尚未得到证实。本研究针对首批100名参与TRACERx肺癌研究的受试者开展个性化循环肿瘤DNA分析，其中1名患者同时被纳入PEACE（Posthumous Evaluation of Advanced Cancer Environment）死后研究项目。研究人员明确了早期非小细胞肺癌患者循环肿瘤DNA释放的独立预测因子，并完成了肿瘤体积检测限分析。通过对术后血浆的盲法测序分析，本研究观察到辅助化疗耐药的相关证据，并可识别出后续将出现肺癌复发的患者。最后，本研究证实系统发育循环肿瘤DNA分析可追踪肺癌复发与转移的亚克隆特征，为基于循环肿瘤DNA的治疗研究提供了全新方法。本研究对应的EGA数据集编号为EGAS00001002415。