Cell-free circulating DNA (cfcDNA) Methylation Quantification as Diagnostic Biomarker of Pheochromocytomas (PCCs) and Paragangliomas (PGLs)

Circulating tumor DNA (ctDNA) is newly diagnostic tumor DNA that can easily represent the genetic and epigenetic change of a tumor. Pheochromocytomas (PCCs) and Paragangliomas (PGLs) are rare tumors of adrenal gland tissue that have the potential to be detected by ctDNA. We aimed to study the potential of the methylation status of RDBP, SDHB, and SDHC genes in ctDNA of PCCs/PGLs patients as a diagnostic biomarker. Clinical data and fresh frozen tissue and blood of 12 PCCs/PGLs patients and blood of 12 age/sex-matched normal patients were collected. The methylation status of RDBP, SDHB, and SDHC was compared between case and controls by MS-HRM analysis. Amongst six promoter regions of RDBP, SDHB, and SDHC, promoter methylation quantification of SDHCa and RDBPb was significantly different between PCCs/PGLs and controls. SDHCa was methylated in 49.93% of PCCs/PGLs cases vs. 8.33 % of control samples, p-value: 0.026, area under curve AUC=0.757, and RDBPb in 74.9% of PCCs/PGLs cases vs. 25.0% of control samples, p-value: 0.032, AUC=0.750. This study suggests the ctDNA potential for a less invasive source of tumor epigenetic modification in PCCs/PGLs malignancies. The SDHCa and RDBPb hypermethylation warrant further exploration as diagnostic tools for PCCs/PGLs.

Author(s): Fatemeh Khatami

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