Multi-omics profiling of primary small cell carcinoma of the esophagus reveals RB1 disruption and additional molecular subtypes

Renda Li, Zhenlin Yang, Fei Shao, Hong Cheng, Yaru Wen, Sijin Sun, Wei Guo, Zitong Li, Fan Zhang, Liyan Xue, Nan Bi, Jie Wang, Yingli Sun, Yin Li, Fengwei Tan, Qi Xue, Shugeng Gao, Susheng Shi (), Yibo Gao () and Jie He ()
Additional contact information
Renda Li: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Zhenlin Yang: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Fei Shao: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Hong Cheng: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yaru Wen: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Sijin Sun: 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
Zitong Li: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Fan Zhang: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Liyan Xue: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Nan Bi: 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
Yingli Sun: Central Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yin Li: 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
Qi Xue: 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
Susheng Shi: 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, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Primary small cell carcinoma of the esophagus (PSCCE) is a lethal neuroendocrine carcinoma. Previous studies proposed a genetic similarity between PSCCE and esophageal squamous cell carcinoma (ESCC) but provided little evidence for differences in clinical course and neuroendocrine differentiation. We perform whole-exome sequencing, RNA sequencing and immunohistochemistry profiling on 46 PSCCE cases. Integrated analyses enable the discovery of multiple mechanisms of RB1 disruption in 98% (45/46) of cases. The transcriptomic landscape of PSCCE closely resembles small cell lung cancer (SCLC) but differs from ESCC or esophageal adenocarcinoma (EAC). Distinct gene expression patterns regulated by ASCL1 and NEUROD1 define two molecular subtypes, PSCCE-A and PSCCE-N, which are highly similar to SCLC subtypes. A T cell excluded phenotype is widely observed in PSCCE. In conclusion, PSCCE has genomic alterations, transcriptome features and molecular subtyping highly similar to SCLC but distinct from ESCC or EAC. These observations are relevant to oncogenesis mechanisms and therapeutic vulnerability.

Date: 2021
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DOI: 10.1038/s41467-021-24043-6

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