Murtaza Muhammed, Dawson Sarah-Jane, Pogrebniak Katherine, Rueda Oscar M, Provenzano Elena, Grant John, Chin Suet-Feung, Tsui Dana W Y, Marass Francesco, Gale Davina, Ali H Raza, Shah Pankti, Contente-Cuomo Tania, Farahani Hossein, Shumansky Karey, Kingsbury Zoya, Humphray Sean, Bentley David, Shah Sohrab P, Wallis Matthew, Rosenfeld Nitzan, Caldas Carlos
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
Department of Oncology, University of Cambridge, Cambridge CB2 0RE, UK.
Nat Commun. 2015 Nov 4;6:8760. doi: 10.1038/ncomms9760.
Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution.
循环肿瘤DNA分析可用于追踪肿瘤负荷并以非侵入性方式分析癌症基因组，但它在多大程度上代表转移异质性尚不清楚。在此，我们跟踪了一名转移性雌激素受体阳性和人表皮生长因子受体2阳性乳腺癌患者，该患者在3年中接受了两线靶向治疗。我们使用外显子组和靶向扩增子测序，对在1193天临床随访期间收集的8份肿瘤活检样本和9份血浆样本的基因组结构进行了表征，并推断了克隆进化。血浆样本中的突变水平反映了从肿瘤活检测序推断出的克隆层次结构。亚克隆私有突变循环水平的系列变化与转移部位之间不同的治疗反应相关。对一名转移性乳腺癌患者的活检样本和血浆样本进行的这种比较表明，循环肿瘤DNA能够对多灶性克隆进化进行实时采样。
