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

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.

SUBMITTER: Li R

PROVIDER: S-EPMC8213753 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Li Renda R Yang Zhenlin Z Shao Fei F Cheng Hong H Wen Yaru Y Sun Sijin S Guo Wei W Li Zitong Z Zhang Fan F Xue Liyan L Bi Nan N Wang Jie J Sun Yingli Y Li Yin Y Tan Fengwei F Xue Qi Q Gao Shugeng S Shi Susheng S Gao Yibo Y He Jie J

Nature communications 20210618 1

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) ...[more]

PMID: 34145257

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Dataset Information

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

Publications

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

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