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Multi-omics profiling of primary small cell carcinoma of the esophagus reveals RB1 disruption and additional molecular subtypes
- Source :
- Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021), Nature Communications
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
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.<br />Primary small cell carcinoma of the oesophagus has a poor prognosis, and has not been fully characterised molecularly. Here, the authors study the disease using multi-omics technology and find frequent RB1 disruptions and similarities to small cell lung cancer, opening potential therapeutic avenues.
- Subjects :
- 0301 basic medicine
Lung Neoplasms
Esophageal Neoplasms
Ubiquitin-Protein Ligases
Science
General Physics and Astronomy
Biology
Adenocarcinoma
medicine.disease_cause
Small-cell carcinoma
Neuroendocrine differentiation
General Biochemistry, Genetics and Molecular Biology
Article
Transcriptome
03 medical and health sciences
0302 clinical medicine
Esophagus
Gene expression
Carcinoma
medicine
Basic Helix-Loop-Helix Transcription Factors
Biomarkers, Tumor
Cancer genomics
Humans
Carcinoma, Small Cell
Tumour-suppressor proteins
neoplasms
Multidisciplinary
Sequence Analysis, RNA
Gene Expression Profiling
Oesophageal cancer
General Chemistry
medicine.disease
Phenotype
Small Cell Lung Carcinoma
Gene expression profiling
Retinoblastoma Binding Proteins
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
Esophageal Squamous Cell Carcinoma
Carcinogenesis
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....082d4d820b645acdc92dc82d2cdb5766