The role of methylation quantification of circulating tumor DNA (ctDNA) as a diagnostic biomarker of Pheochromocytomas (PCCs) and Paragangliomas (PGLs)

Fatemeh Khatami; Leonardo Oliveira Reis; Mehdi Ebrahimi; Shirzad Nasiri; Seyed Mohammad Tavangar; Mahin Ahmadi Pishkuhi; Gita Shafiee; Ramin Heshmat; Seyed Mohammad Kazem Aghamir

doi:10.1007/s40200-024-01466-8

The role of methylation quantification of circulating tumor DNA (ctDNA) as a diagnostic biomarker of Pheochromocytomas (PCCs) and Paragangliomas (PGLs)

J Diabetes Metab Disord. 2024 Jul 20;23(2):2065-2072. doi: 10.1007/s40200-024-01466-8. eCollection 2024 Dec.

Authors

Fatemeh Khatami¹, Leonardo Oliveira Reis², Mehdi Ebrahimi³, Shirzad Nasiri⁴, Seyed Mohammad Tavangar⁵, Mahin Ahmadi Pishkuhi^{1

6}, Gita Shafiee⁷, Ramin Heshmat⁷, Seyed Mohammad Kazem Aghamir¹

Affiliations

¹ Urology Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan Abad Sq., Imam Khomeini Ave, Tehran, Iran.
² UroScience and Department of Surgery (Urology), School of Medical Sciences, University of Campinas, Unicamp, and Pontifical Catholic University of Campinas, PUC-Campinas, Campinas, São Paulo, Brazil.
³ Department of Internal Medicine, Faculty of Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Departments of Surgery, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran.
⁵ Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, University of Medical Science, Tehran, Iran.
⁷ Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

PMID: 39610555
PMCID: PMC11599490 (available on 2025-07-20)
DOI: 10.1007/s40200-024-01466-8

Abstract

Objectives: Circulating tumor DNAs (ctDNAs) are fragments of malignant tissue DNA that can simply signify the real time genetic change and epigenetic modification of a solid tumor tissue. Pheochromocytomas (PCCs) and Paragangliomas (PGLs) are malinancy of adrenal gland tissue that have the possible diagnosis by ctDNAs. In this study the methylation quanifcation of three target genes RDBP, SDHB, and SDHC in the ctDNA of PCCs/PGLs patients were measured as a diagnostic biomarker.

Methods: The biological samples include blood and fresh frozen tissue of twelve PCCs/PGLs patients and blood of 12 non tumoral patients as controls were recruited. Semi quantification methylation status of RDBP, SDHB, and SDHC (two CpG lslands of each gene named 1 and 2) was assesed between PCCs/PGLs patients and controls by Methylation specific-high resolution melting (MS-HRM) technique.

Results: Between six candidate CpG island of RDBP, SDHB, and SDHC, promoter methylation quantification of SDHC1 and RDBP2 was expressively unsimilar in PCCs/PGLs compare to the controls. SDHC1 was hypermethylated in 49.93% of PCCs/PGLs cases vs. 8.33% of control samples, p-value: 0.026, area under curve AUC = 0.757, and RDBP2 in 74.9% of PCCs/PGLs cases vs. 25.0% of control samples, p-value: 0.032, AUC = 0.750.

Conclusions: Our result shows that the ctDNA hypermethylation of SDHC1 and RDBP2 have role in tumorgenesis of adrenal gland and can consider for diagnosis of PCCs/PGLs.

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-024-01466-8.

Keywords: Liquid biopsy; Methylation; Paraganglioma; Pheochromocytoma; RDBP2; SDHC1; ctDNA.

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