The applications of circulating cell-free DNA for oral squamous cell carcinoma patients as non-invasive diagnostics of structural variants, fusions and oncoviruses

Abstract

Circulating cell-free DNA (cfDNA) has been widely used as a prognostic marker of different cancers. In this study, we used cfDNA from oral squamous cell carcinoma (OSCC) patients to study various correlation factors that could improve early-stage diagnostics and prognosis. We found that OSCC patient cfDNA concentration can serve as an indicator of tumor stage, malignancy, and survival prognosis. Deep genome sequencing of cfDNA revealed genomic alterations, such as copy number variation, fusion gene identification, and viral integration. Copy number variation analysis suggested correlation with amplification and deletions in chromosome 1 at loci 1q, 2q, 3p, 3q and 8q22. Moreover, at these loci, amplification ofTP53, PIK3CAand other genes related to keratinization in relapsed OSCC was observed. In addition, we identified a novel fusion gene,TRMO-TRNT1, in seven high-grade tumor samples. The parent genes of this chimera,TRMOandTRNT1, are known to play roles in tRNA modification and DNA repair. Liquid biopsy may thus serve as a sensitive tool to study OSCC patient genomic alterations by addressing cfDNA circulating in the plasma, using an easy-to-use blood test. Finally, we detected integrations of human papilloma virus, simian virus and enterovirus that may point to the origins of OSCC.