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ePoster Display

40P - Evolutionary trajectories and clonal migration underlying tumor progression and lymph node metastasis in resectable lung cancer


16 Sep 2021


ePoster Display


Rong Yin


Annals of Oncology (2021) 32 (suppl_5): S361-S375. 10.1016/annonc/annonc684


R. Yin1, S. Wang1, C. Wang2, J. Zhang3, M. Li1, F. Jiang1, X. Fan4, M. Wu4, H. Bao4, R. Yu4, X. Wu4, Y. Shao4, L. Xu1

Author affiliations

  • 1 Department Of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, 210009 - Nanjing/CN
  • 2 Department Of Epidemiology And Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, 211116 - Nanjing/CN
  • 3 Department Of Pathology, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, 210009 - Nanjing/CN
  • 4 Department Of Research And Development, Nanjing Geneseeq Technology Inc., 210032 - Nanjing/CN

Abstract 40P


Progression and metastasis of early-to-mid stage lung cancers exhibited great diversity and have not been systemically studied to date. Evolutionary genomics underlying lung cancer progression and metastasis may provide guidance for patient stratification and personalized disease management.


We collected 160 primary tumors (PTs, 474 regions) and 112 lymph node metastases (LNMs) from 125 patients with stage I-III resectable lung cancer and performed targeted sequencing. We reconstructed the sample phylogeny of each patient and investigated evolutionary subtypes of PTs and metastatic trajectories of LNMs at the clonal resolution.


In progressive clonal evolution of PTs, intratumor heterogeneity decreased with tumor growth while clonal diversity increased with tumor differentiation. NF1 and RB1 mutations were selected during clonal sweep. We categorized lung adenocarcinomas into 7 evolutionary subtypes and elaborated their correlation with clinicopathological features. Subtypes with late-acquired TP53 mutations indicated worse DFS than those initiated by TP53 mutations (HR = 7.98; P = 0.0070). We further identified NF1 and TP53 mutations as potent metastatic drivers and unfavored prognostic markers for metastasis-free patients (P = 0.021 and 0.0017, respectively). An overall trend of sequential metastatic spreading was observed, on the basis of which we engraved fine classifications of seeding modes by clonality and trajectories. The majority of LNMs (67.9%) were seeded multiclonally, among which three cases showed profound evidence for LN-mediated metastasis. Moreover, multiple metastases of distinct evolutionary origins indicated higher risk of relapse than those of common origins.


Our results depict the evolutionary patterns of PTs and LNMs in patients with resectable lung cancers. Features such as evolutionary subtypes of PTs and phylogenetic origins of LNMs may serve as prognostic markers for optimal treatment in lung cancer patients. Our study highlights the clinical significance of evolutionary genomics in the understanding of tumor progression and disease management.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research.


Key Project of Cutting-edge Clinical Technology of Jiangsu Province (BE2016797); National Science Foundation of China (81872378, 81672295, 81572261, 81501977); The Project of Jiangsu Provincial Medical Talent (ZDRCA2016033).


X. Fan, M. Wu, H. Bao, R. Yu, X. Wu, Y. Shao: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. All other authors have declared no conflicts of interest.

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