Integrated molecular characterization reveals potential therapeutic strategies for pulmonary sarcomatoid carcinoma

Zhenlin Yang, Jiachen Xu, Lin Li, Renda Li, Yalong Wang, Yanhua Tian, Wei Guo, Zhijie Wang, Fengwei Tan, Jianming Ying, Yuchen Jiao, Shugeng Gao (), Jie Wang (), Yibo Gao () and Jie He ()
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Zhenlin Yang: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Jiachen Xu: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Lin Li: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Renda Li: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yalong Wang: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yanhua Tian: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Wei Guo: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Zhijie Wang: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Fengwei Tan: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Jianming Ying: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yuchen Jiao: State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Shugeng Gao: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Jie Wang: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yibo Gao: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Jie He: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer with poor prognosis. Here, we perform multi-omics analysis of 56 PSC samples, 14 of which are microdissected to analyze intratumoral heterogeneity. We report the mutational landscape of PSC. The epithelial and sarcomatoid components share numerous genomic alterations, indicating a common progenitor. We find that epithelial-mesenchymal transition (EMT) plays important roles in the carcinogenesis of PSC. The pan-cancer analysis reveals high tumor mutation burden and leukocyte fraction of PSC. Integrated molecular classification shows three subgroups with distinct biology, prognosis and potential therapeutic strategies. Actionable mutations are enriched in C1 and C2, patients in C3 have a significantly longer overall survival, and C1 and C2 exhibit T-cell inflamed microenvironments. The three subgroups show molecular similarities to specific subtypes of conventional lung cancer. In conclusion, our study reveals the molecular characteristics and provides entry points for the treatment of PSC.

Date: 2020
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DOI: 10.1038/s41467-020-18702-3

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