伦敦大学学院癌症研究所Mariam Jamal-Hanjani小组取得一项新突破。他们研制了肺癌转移的进化特征。该研究于2026年4月29日发表于国际一流学术期刊《自然》杂志上。

主题501纵向收集了24例非小细胞肺癌（NSCLC）患者的原发和转移性肿瘤样本，这些患者参加了TRACERx肺部研究和PEACE尸检计划，该研究组推断了肿瘤从诊断到死亡的演变。DNA测序数据涵盖了死亡前放射学检测到的70%的转移瘤和配对的多区域原发性肿瘤样本，该研究团队发现转移瘤的基因组与其祖先原发性肿瘤的基因组明显不同，在转移传播后发生了额外的驱动改变和基因组倍增事件。在62.5%的患者中，多个原发肿瘤亚克隆播散，每个亚克隆都有不同的转移。这些转移瘤是继续扩散的标志：超过一半的转移瘤是由其他转移瘤播撒的。原位转移的持续时间影响其播散进一步转移的可能性。大多数转移性迁移开始和结束于同一解剖腔。少数离开胸腔转移的亚克隆广泛播散，并因体细胞拷贝数改变而富集，表明染色体不稳定性可能促进胸外扩散。这种时空进化分析揭示了晚期非小细胞肺癌的转移多样性和播种程度，这在单一转移活检中往往被低估，并确定了转移进展的基因组和临床介质。

据了解，对控制转移性扩散的生物学过程的有限理解阻碍了其预防和治疗。

附：英文原文

Title: Evolutionary characterization of lung cancer metastasis

Author: Hessey, Sonya, Bunkum, Abigail, Huebner, Ariana, Haase, Kerstin, Grigoriadis, Kristiana, Naceur-Lombardelli, Cristina, Liu, Wing Kin, Harrigan, Caitlin F., Grieco, Charlotte, Marinelli, Daniele, Ding, Boyue, Martnez-Ruiz, Carlos, Pawlik, Piotr, Hill, Mark S., Lucas, Olivia, Richard, Corentin, Pich, Oriol, Thol, Kerstin, Karasaki, Takahiro, Ward, Sophia, Athanasopoulou, Foteini, Sivakumar, Monica, Veeriah, Selvaraju, Toncheva, Antonia, Rowan, Andrew J., Prymas, Paulina, Bridger, Hayley, Mitchison, Miriam, Borg, Elaine, Falzon, Mary, Proctor, Ian, Mahadeva, Ula, Green, Anna, Forster, Martin D., Benafif, Sarah, Ahmad, Tanya, Lee, Siow Ming, Papadatos-Pastos, Dionysis, Naidu, Babu, Langman, Gerald, Krebs, Matthew G., Oliveira, Pedro, Blackhall, Fiona H., Summers, Yvonne, Weaver, Jamie, Le Quesne, John, Thomas, Anne, Richards, Cathy, Fennell, Dean A., Jogai, Sanjay, Cave, Judith, Roxburgh, Patricia, Fraser, Sioban, Kirk, Alan, Blyth, Kevin G.

Issue&Volume: 2026-04-29

Abstract: Limited understanding of the biological processes that govern metastatic dissemination hinders its prevention and treatment1. Here, using 501 longitudinally collected primary and metastatic tumour samples from 24 patients with non-small cell lung cancer (NSCLC) enrolled in the TRACERx lung study and PEACE autopsy programme, we infer tumour evolution from diagnosis to death. With DNA-sequencing data encompassing 70% of the metastases that were radiologically detected before death and paired multi-region sampled primary tumours, we show that the genomes of metastases diverge markedly from those of their ancestral primary tumour, with additional driver alterations and genome doubling events occurring after metastatic dissemination. In 62.5% of patients, multiple primary tumour subclones disseminated, each founding a distinct metastasis. These metastases served as sources of onward spread: more than half of the metastases sampled were seeded by other metastases. The duration that metastases existed in situ influenced their likelihood of seeding further metastases. Most metastatic migrations started and ended in the same anatomical cavity. The few subclones that exited the thorax to seed metastases disseminated widely and were enriched for somatic copy-number alterations, suggesting that chromosomal instability may facilitate extrathoracic spread. This spatial and temporal evolutionary analysis sheds light on the extent of metastatic diversity and seeding in advanced NSCLC—which tends to be underestimated in single metastasis biopsies—and identifies genomic and clinical mediators of metastatic progression.

DOI: 10.1038/s41586-026-10428-4

Source: https://www.nature.com/articles/s41586-026-10428-4