Detection of Circulating Tumor-specific DNA Methylation Markers in the Blood of Patients with Pituitary Tumors.

Abstract Genome-wide DNA methylation aberrations are pervasive and associated with clinicopathological features across pituitary tumors (PT) subtypes. The feasibility to detect CpG methylation abnormalities in circulating cell-free DNA (cfDNA) has been reported in central nervous system tumors other than PT. Here, we aimed to profile and identify methylome-based signatures in the serum of patients harboring PT (n=13). Our analysis indicated that serum cfDNA methylome from patients with PT are distinct from the counterparts in patients with other tumors (gliomas, meningiomas, colorectal carcinomas, n=124) and nontumor conditions (n=4). Furthermore, the serum methylome patterns across PT was associated with functional status and adenohypophyseal cell lineage PT subtypes, recapitulating epigenetic features reported in PT-tissue. A machine learning algorithm using serum PT-specific signatures generated a score that distinguished PT from non-PT conditions with 100% accuracy in our validation set. These preliminary results underpin the potential clinical application of a liquid biopsy-based DNA methylation profiling as a noninvasive approach to identify clinically relevant epigenetic markers that can be used in the management of PT.