Related Experiment Video
Updated: Jun 4, 2025
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Emerging molecular phenotypes and potential therapeutic targets in esophageal and gastric adenocarcinoma unearthed by
Annika Windon1, Majd Al Assaad2, Kevin Hadi3
1Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Background:
Adenocarcinoma of the esophagus and stomach demands a deeper molecular understanding to advance treatment strategies and improve patient outcomes. Here, we profiled the genome and transcriptome landscape of these cancers, explored molecular characteristics that are undetectable by other sequencing platforms, and analyzed their potential clinical ramifications.
Methods:
Our study employed state-of-the-art integrative analyses of whole genome and transcriptome sequencing on 51 matched tumor and germline samples from 46 patients. Mutations and rearrangements in clinically relevant cancer genes were investigated and correlated with OncoKB, a knowledge-based precision oncology database, to identify treatment implications. Genome-wide signatures and manually curated molecular profiles were also determined.
Results:
The analyses revealed 90 targetable oncogenic mutations and fusions in 63 % of the patients, including novel NTRK, NRG1, ALK, and MET fusions, and structural variants in cancer genes like RAD51B. Also, molecular signatures associated with mismatch repair and homologous recombination deficiency were elucidated. Notably, we identified CDK12-type genomic instability associated with CDK12 fusions.
Conclusions:
Our findings support the potential of whole genome and transcriptome sequencing analyses as a comprehensive approach to identify treatment targets in adenocarcinoma of the stomach and the esophagus, and their application in precision oncology.
Insights
Comprehensive genomic and transcriptome sequencing identified 90 targetable mutations and fusions in 63% of esophageal and stomach adenocarcinoma patients, revealing new treatment targets for precision oncology.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Esophageal and stomach adenocarcinomas require enhanced molecular insights for improved treatments.
- Current understanding of these cancers' molecular landscape is limited.
Purpose of the Study:
- To profile the genome and transcriptome of esophageal and stomach adenocarcinomas.
- To identify novel molecular characteristics and potential clinical implications for treatment strategies.
Main Methods:
- Integrative analysis of whole genome and transcriptome sequencing on 51 matched tumor and germline samples.
- Correlation of mutations and rearrangements with the OncoKB precision oncology database.
- Determination of genome-wide signatures and molecular profiles.
Main Results:
- Identified 90 targetable oncogenic mutations and fusions in 63% of patients, including novel NTRK, NRG1, ALK, and MET fusions.
- Detected structural variants in cancer genes such as RAD51B.
- Elucidated molecular signatures for mismatch repair and homologous recombination deficiency, and CDK12-type genomic instability.
Conclusions:
- Whole genome and transcriptome sequencing offer a comprehensive approach for identifying treatment targets.
- These analyses hold significant potential for advancing precision oncology in esophageal and stomach adenocarcinomas.
