23. Detection of somatic tumor mutations in circulating plasma DNA of patients with sellar and skull base tumors

Abstract

The use of cell-free DNA (cfDNA) as a liquid biopsy is a promising clinical tool that allows for earlier detection of cancer, advanced therapeutic monitoring, and can even predict treatment outcomes. Its feasibility has been shown in lung, breast and prostate cancers, but there is a lack of investigation in rare CNS tumors which present unique challenges in treatment and surgical accessibility. Preoperative profiling of these tumors could help guide personalized treatment options. We performed Whole Exome Sequencing (WES) on matched plasma cell-free DNA and tumor DNA of 15 patients with CNS tumors resected at the University of Washington Medical Center. This cohort includes pituitary neuroendocrine tumors (pitNETs) which are the most common intracranial neoplasms, as well as rare tumors- craniopharyngiomas and recurrent and high-grade meningiomas. Somatic variant calling revealed an average of 368 mutations in the tumors alone, while cfDNA from the plasma harbored an average of 298,839 somatic mutations. We compared the genomic profiles of cfDNA and the respective tumor sample. A total of 11 exonic non-synonymous variants (7 SNVs, 4 INDELs) in 9 different genes were detected in matched cfDNA and tumor. Mutations on the CSPG4 and GOLGA6L9 genes were validated in 13 samples of a larger cohort of PitNET genomic DNA (n=66) and may serve as potential markers for pitNETs and their subtypes. Here we show that somatic shared somatic mutations in cfDNA and matching tumor tissue can be successfully identified through WES, demonstrating that liquid biopsy might be a feasible approach for PitNETs.