Molecular characterization of the evolution of premalignant lesions in the upper aerodigestive tract
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View abstract on PubMed
Summary
This summary is machine-generated.Genomic and immune changes occur early in head and neck squamous cell carcinoma (HNSCC) evolution. Understanding these early alterations in premalignant lesions can help predict and prevent cancer progression.
Area Of Science
- Oncology
- Genomics
- Immunology
Background
- Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis due to early relapse and metastasis.
- HNSCC arises from genetically altered cells in premalignant fields, but predicting progression remains a challenge.
- Understanding molecular mechanisms is crucial for reducing HNSCC morbidity and mortality.
Purpose Of The Study
- To analyze the genome and immune microenvironment of normal, premalignant, and cancerous tissues in HNSCC.
- To identify early molecular events driving HNSCC progression in p16-negative cases.
Main Methods
- Targeted Next-Generation Sequencing (161 genes) and shallow whole-genome sequencing were performed on matched tissue samples.
- Nanostring PanCancer Immune Panel was used to analyze the immune microenvironment.
- Samples included normal squamous tissue, premalignant lesions, and primary/recurrent tumors from seven patients.
Main Results
- TP53 and NOTCH1 were the most frequently mutated genes.
- Genomic instability increased from normal mucosa to high-grade dysplasia, with rearranged genomes similar to invasive carcinoma.
- Interferon pathway genes were upregulated early in dysplasia, and SPINK5 was downregulated even in low-grade lesions.
Conclusions
- Genomic alterations and aberrant immune gene expression are detectable early in upper aerodigestive tract tumor evolution.
- These early changes offer potential targets for therapeutic intervention to prevent HNSCC progression.
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