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Updated: Feb 13, 2026

3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
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Comprehensive genomic profiling of neuroendocrine bladder cancer pinpoints molecular origin and potential

Peiye Shen1,2, Ying Jing1, Ruiyun Zhang3

  • 1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Oncogene
|March 15, 2018
PubMed

Insights

Neuroendocrine bladder cancer shares genetic similarities with urothelial carcinoma, suggesting a common origin. Genomic analysis revealed targetable mutations and potential mechanisms driving this rare, lethal malignancy.

Area of Science:

  • Oncology
  • Genomics
  • Urology

Background:

  • Neuroendocrine bladder cancer is a rare, aggressive malignancy with poorly understood origins and treatment.
  • Existing knowledge on its oncogenomic landscape and cellular origins is limited.

Purpose of the Study:

  • To perform comprehensive genomic and transcriptomic sequencing on neuroendocrine bladder neoplasms.
  • To elucidate the mutational landscape, cellular origin, and potential therapeutic targets in neuroendocrine bladder cancer.

Main Methods:

  • Whole-genome and transcriptome sequencing of genitourinary neuroendocrine neoplasms, primarily small cell bladder carcinomas.
  • Analysis of mutational landscape, signatures, fusion transcripts, and gene expression.
  • Investigating the role of TP53 and RB1 depletion in lineage switching.

Main Results:

  • Neuroendocrine bladder cancer exhibits mutational patterns similar to urothelial carcinoma, supporting a common cell of origin.
  • Identified age-related and APOBEC-mediated mutagenesis, and aristolochic acid exposure signature.
  • Discovered novel fusion transcripts, including a targetable PVT1-ERBB2 variant impacting HER2 expression.
  • TP53 and RB1 depletion promoted lineage switching and reduced sensitivity to targeted therapies.

Conclusions:

  • This study provides the first high-resolution genomic portrait of neuroendocrine bladder cancer.
  • Findings suggest a common origin with urothelial carcinoma and reveal potential therapeutic vulnerabilities.
  • Understanding the genomic underpinnings is crucial for developing effective treatments for this deadly disease.

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