The genomic architechtures of tumor-adjacent tissues, plasma and saliva reveal evolutionary underpinnings of relapse in head and neck squamous cell carcinoma.

e18046 Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by dismal prognosis, nonetheless limited studies have unveiled the mechanisms underlying HNSCC relapse. Methods: Next-generation sequencing 1 5 was performed to identify somatic mutations in 188 matched samples including primary tumors, tumor adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. Evolutionary relationship between TATs and tumors were analyzed. The dynamic changes of tumor- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis. Results: Alterations were detected in 27/27 and 19/26 tumors and TATs respectively. TP53 was the most prevalent genes mutated in TATs. Some TATs shared mutations with primary tumors, while some other TATs were evolutionarily unrelated to tumors. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and indicative of worse survival (HR=14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies, and indicative of disease relapse. Conclusions: TATs might undergo the processes of premalignant transformation, tumorigenesis, and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where tumor originated or gaining private mutations independent to primary tumor. Detection of tumor- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use.