ena-STUDY-Kyoto University-24-04-2018-14:59:18:717-483
Age-related remodeling of apparently normal esophageal epithelia by common cancer drivers
Esophageal squamous cell carcinoma develops in significant association with chronic exposure to drinking and smoking, frequently in a metachronous manner.  To understand the genetic basis of clonal evolutions and their field effect contributions toward ESCC, we conducted multi-region sequencing in apparently normal non-dysplasia and dysplasia/cancer esophageal tissues.  Mutations were identified in 96.9% of non-dysplasticnormal tissues, where NOTCH1, TP53 were significantly mutated.  In dysplasia and cancer, NOTCH1 mutations were less frequent, whereas TP53 mutations and focal copy number lesions were dominant.  Additional micrometer-resolution normal epitheliumnon-dysplasia analyses revealed bi-allelic NOTCH1 and TP53 mutations.  The molecular profiles correlated strongly with alcohol- and smoking-related mutational signatures at all pathological stages, with an APOBEC-related signature predominant in cancer.  ENon-dysplastic esophageal normal tissues of alcohol- and tobacco-consuming patients highlight genetically distinct non-cancerous clonal expansion.
Esophageal squamous cell carcinoma develops in significant association with chronic exposure to drinking and smoking, frequently in a metachronous manner.  To understand the genetic basis of clonal evolutions and their field effect contributions toward ESCC, we conducted multi-region sequencing in apparently normal non-dysplasia and dysplasia/cancer esophageal tissues.  Mutations were identified in 96.9% of non-dysplasticnormal tissues, where NOTCH1, TP53 were significantly mutated.  In dysplasia and cancer, NOTCH1 mutations were less frequent, whereas TP53 mutations and focal copy number lesions were dominant.  Additional micrometer-resolution normal epitheliumnon-dysplasia analyses revealed bi-allelic NOTCH1 and TP53 mutations.  The molecular profiles correlated strongly with alcohol- and smoking-related mutational signatures at all pathological stages, with an APOBEC-related signature predominant in cancer.  ENon-dysplastic esophageal normal tissues of alcohol- and tobacco-consuming patients highlight genetically distinct non-cancerous clonal expansion.