Clonal dynamics and Stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma

npj Precision Oncology

Article

Sha Liao¹  Jiajun Zhang¹  Fei Teng²  Jikai Zhao³  Zhanxian Shang³  Yuchen Han³  Ruiying Zhao³  Shengnan Chen³  Chan Xiang³  Yedan Chen⁴  Hairong Bao⁴  Hua Bao⁴  Qian Wu⁴  Jiaohui Pang⁴  Yang Shao⁵  Shun Lu⁶  Yunhua Xu⁶ 

[1] BGI Research, 401329, Chongqing, PR China;BGI Research, 518083, Shenzhen, PR China;BGI Research, 518083, Shenzhen, PR China;Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, Shanghai, PR China;Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., 210032, Nanjing, PR China;Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., 210032, Nanjing, PR China;School of Public Health, Nanjing Medical University, 211166, Nanjing, PR China;Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, Shanghai, PR China;

关键词: ;   

DOI  :  10.1038/s41698-023-00430-8

 received in 2023-02-16, accepted in 2023-07-31,  发布年份 2023

来源: Springer

【 摘 要 】

The genomic origin and development of the biphasic lung adenosquamous carcinoma (ASC) remain inconclusive. Here, we derived potential evolutionary trajectory of ASC through whole-exome sequencing, Stereo-seq, and patient-derived xenografts. We showed that EGFR and MET activating mutations were the main drivers in ASCs. Phylogenetically, these drivers and passenger mutations found in both components were trunk clonal events, confirming monoclonal origination. Comparison of multiple lesions also revealed closer genomic distance between lymph node metastases and the ASC component with the same phenotype. However, as mutational signatures of EGFR-positive lung squamous carcinomas (LUSCs) were more comparable to EGFR-positive ASCs than to wild-type LUSCs, we postulated different origination of these LUSCs, with ASC being the potential intermediate state of driver-positive LUSCs. Spatial transcriptomic profiling inferred transformation from adenocarcinoma to squamous cell carcinoma, which was then histologically captured in vivo. Together, our results explained the development of ASC and provided insights into future clinical decisions.

【 授权许可】

CC BY   
© Nature Publishing Group UK 2023

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