Comparison of Somatic Mutations in Primary Squamous Cell Carcinomas of the Hypopharynx and the Esophagus Developed in Individual Patients

BACKGROUND: Hypopharyngeal squamous cell carcinoma (HPSCC) and esophageal squamous cell carcinoma (ESCC) share common risk factors such as alcohol consumption and smoking, leading to synchronous or metachronous diseases. METHODS: We analyzed 24 formalin-fixed paraffin-embedded tissue specimens of surgically treated HPSCC and ESCC from 12 Japanese patients. Targeted sequencing of 409 cancer-related genes was conducted and mutational signatures were assessed. RESULTS: Most frequent somatic driver mutation identified was in TP53 (39.5%). Although driver mutations were detected in the same genes in seven patients, no identical clonal mutations were identified between HPSCC and ESCC. Eight patients had either heterozygous or homozygous polymorphisms of aldehyde dehydrogenase 2 (ALDH2) associated with reduced enzymatic activity. The mutational signature analysis showed SBS5 and SBS18 mutation patterns. CONCLUSIONS: The present findings suggest that common somatic mutations of TP53 in conjunction with ALDH2 polymorphisms contribute to the development of synchronous and metachronous HPSCC and ESCC.