The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.
The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.
复制标题
DOI：
10.1158/1078-0432.ccr-17-3374
复制
发表时间：
2018-10-01
期刊：
影响因子：
--
通讯作者：
Sottoriva A
中科院分区：
文献类型：
--
作者：
Barry P;Vatsiou A;Spiteri I;Nichol D;Cresswell GD;Acar A;Trahearn N;Hrebien S;Garcia-Murillas I;Chkhaidze K;Ermini L;Huntingford IS;Cottom H;Zabaglo L;Koelble K;Khalique S;Rusby JE;Muscara F;Dowsett M;Maley CC;Natrajan R;Yuan Y;Schiavon G;Turner N;Sottoriva A
早期乳腺癌中最重要的预后因素是淋巴结受累。
在11个没有临床证据的乳腺癌阳性阳性阳性的阳性阳性阳性的阳性阳性证据中，我们使用了原代和淋巴结沉积物的空间多区域测序（n = 78个样本）研究了淋巴结的进化，以及匹配的纵向循环肿瘤DNA（CTDNA）的基因组沉积物和基因组分析。
从原发性到淋巴结的线性进化很少见（1/11），而大多数病例在原发性和节点之间表现出早期差异（4/11），或者没有可检测的差异（6/11），主要细胞均属于转移性clone的差异。优雅的等离子体术手部服用反映了两种主要的进化模式，并证明即使从早期的转移性淋巴结沉积物中也可以检测到私有突变。
这项研究为乳腺癌的自然史上的关键进化步骤提供了新的启示，这表明在很大一部分患者中早期建立了腋窝淋巴结转移。
The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localised and systemic disease is key to understanding breast cancer progression, however our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data derive from primary tumours. In 11 treatment-naïve node positive early breast cancer patients without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multi-region sequencing (n=78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumour DNA (ctDNA). Linear evolution from primary to lymph node was rare (1/11) whereas the majority of cases displayed either early divergence between primary and nodes (4/11), or no detectable divergence (6/11) where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 of 7 subjects with evaluable plasma taken peri-operatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA. This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients.