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Development of Compendium for Esophageal Squamous Cell Carcinoma
03:36

Development of Compendium for Esophageal Squamous Cell Carcinoma

Published on: April 12, 2024

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Multi-region sequencing unveils novel actionable targets and spatial heterogeneity in esophageal squamous cell

Ting Yan1,2, Heyang Cui1,2, Yong Zhou1,2

  • 1Shenzhen Peking University-The Hong Kong University of Science and Technology (PKU-HKUST) Medical Center, Peking University Shenzhen Hospital, 518035, Shenzhen, PR China.

Nature Communications
|April 13, 2019
PubMed

Insights

This study reveals high intra-tumor heterogeneity in esophageal squamous cell carcinoma (ESCC), identifying ERBB4 mutations and BRCA1/2 variants as potential therapeutic targets. Findings may offer new insights for ESCC treatment strategies.

Area of Science:

  • Oncology
  • Genomics
  • Cancer Research

Background:

  • Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer death in China, with limited actionable molecular targets.
  • Understanding tumor heterogeneity is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the genomic landscape and T-cell receptor (TCR) repertoire in multi-regional ESCC tumors.
  • To identify potential actionable molecular targets and biomarkers for ESCC treatment.

Main Methods:

  • Whole-exome and TCR repertoire sequencing were performed on tumor, normal tissue, and blood samples from 39 ESCC patients.
  • Functional studies were conducted to validate the oncogenic role of identified mutations.
  • A large independent cohort (n=508) was used for validation.

Main Results:

  • ERBB4 mutations were found in 12.8% of patients, with functional studies supporting its oncogenic role.
  • 18% of patients with early BRCA1/2 variants showed a high contribution of signature 3, and BRCA1/2 knockdown increased cisplatin sensitivity.
  • Focal amplification of CD274 (PD-L1) was observed in 5% of patients, suggesting potential sensitivity to immune checkpoint blockade.
  • A strong correlation between genomic and TCR repertoire intra-tumor heterogeneity (ITH) was identified.

Conclusions:

  • ESCC exhibits significant intra-tumor heterogeneity.
  • ERBB4, BRCA1/2, and CD274 (PD-L1) represent potential actionable targets for ESCC therapy.
  • The study provides novel insights into ESCC pathogenesis and treatment strategies.

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