Succinate-to-Fumarate Ratio as a New Metabolic Marker to Detect the Presence of SDHB/D-related Paraganglioma: Initial Experimental and Ex Vivo Findings

• DOI: 10.1210/en.2013-1549
• Publication Date: 2013-11-05T04:13:53Z
• Authors: Nikoletta Lendvai; Robert Pawlosky; Petra Bullova; Graeme Eisenhofer; Attila Patocs; Richard L. Veech; Karel Pacak
• Keywords: SDHB; SDHD

Pheochromocytomas (PHEOs) and paragangliomas (PGLs; extra-adrenal tumors) are rare neuroendocrine chromaffin cell tumors with a hereditary background in about 30%-35%. Those caused by succinate dehydrogenase subunit B (SDHB) germline mutations associated high metastatic potential ultimately higher patient mortality. Succinate converts to fumarate, uniquely linking the Krebs cycle oxidative phosphorylation. SDH result accumulation of various metabolic disturbances shift aerobic glycolysis tumor tissue. In present study, we measured fumarate levels mouse pheochromocytoma (MPC) tissue (MTT) cells 10 apparently sporadic, SDHB-, 5 SDHD-, 2 neurofibromatosis 1-related PHEOs/PGLs plasma samples using mass spectrometry. We found that succinate-to-fumarate ratio was significantly SDHB- SDHD-related PGLs than sporadic (P = .0376). To further support our data, silenced SDHB expression MPC MTT evaluated levels. Compared control samples, SDHB-silenced also showed an increase (MTT cells: 2.45 vs 7.53), similar findings SDHB-related PGLs. The for first time demonstrate increased SDHB/D-related thus suggest this may be used as new marker detection PHEOs/PGLs.