Data from: Origins of lymphatic and distant metastases in human colorectal cancer

The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal cancer. Studying 213 archival biopsy samples from 17 patients, we used somatic variants in hypermutable DNA regions to reconstruct high-confidence phylogenetic trees. We found that in 65% of cases, lymphatic and distant metastases arose from independent subclones in the primary tumor, whereas in 35% of cases they shared common subclonal origin. Therefore, two different lineage relationships between lymphatic and distant metastases exist in colorectal cancer.癌细胞从原发肿瘤扩散至区域淋巴结，通常与患者生存期缩短密切相关。针对这一关联的主流模型认为，致命性远处转移灶由淋巴结转移灶定植形成。该观点为TNM分期系统（TNM staging system）提供了机制层面的理论支撑，同时也是肿瘤引流淋巴结外科切除术的核心理论依据。本研究针对人类结直肠癌的原发肿瘤、淋巴结转移灶及远处转移灶之间的演化关系展开探究。我们纳入17名患者的213份存档活检样本，借助高突变DNA区域中的体细胞变异重构了高置信度的系统发育树。研究结果显示，65%的病例中，淋巴转移灶与远处转移灶起源于原发肿瘤内的独立亚克隆；而35%的病例中，二者共享共同的亚克隆起源。因此，结直肠癌中淋巴转移灶与远处转移灶存在两种不同的谱系关系。