Details

Autor(en) / Beteiligte

• Lussey-Lepoutre, Charlotte
• Bellucci, Alexandre
• Morin, Aurélie
• Buffet, Alexandre
• Amar, Laurence
• Janin, Maxime
• Ottolenghi, Chris
• Zinzindohoué, Franck
• Autret, Gwennhael
• Burnichon, Nelly
• Robidel, Estelle
• Banting, Benjamin
• Fontaine, Sébastien
• Cuenod, Charles-André
• Benit, Paule
• Rustin, Pierre
• Halimi, Philippe
• Fournier, Laure
• Gimenez-Roqueplo, Anne-Paule
• Favier, Judith
• Tavitian, Bertrand

Titel

In Vivo Detection of Succinate by Magnetic Resonance Spectroscopy as a Hallmark of SDHx Mutations in Paraganglioma

Ist Teil von

• Clinical cancer research, 2016-03, Vol.22 (5), p.1120-1129

Ort / Verlag

United States: American Association for Cancer Research

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Germline mutations in genes encoding mitochondrial succinate dehydrogenase (SDH) are found in patients with paragangliomas, pheochromocytomas, gastrointestinal stromal tumors, and renal cancers. SDH inactivation leads to a massive accumulation of succinate, acting as an oncometabolite and which levels, assessed on surgically resected tissue are a highly specific biomarker of SDHx-mutated tumors. The aim of this study was to address the feasibility of detecting succinate in vivo by magnetic resonance spectroscopy. A pulsed proton magnetic resonance spectroscopy ((1)H-MRS) sequence was developed, optimized, and applied to image nude mice grafted with Sdhb(-/-) or wild-type chromaffin cells. The method was then applied to patients with paraganglioma carrying (n = 5) or not (n = 4) an SDHx gene mutation. Following surgery, succinate was measured using gas chromatography/mass spectrometry, and SDH protein expression was assessed by immunohistochemistry in resected tumors. A succinate peak was observed at 2.44 ppm by (1)H-MRS in all Sdhb(-/-)-derived tumors in mice and in all paragangliomas of patients carrying an SDHx gene mutation, but neither in wild-type mouse tumors nor in patients exempt of SDHx mutation. In one patient, (1)H-MRS results led to the identification of an unsuspected SDHA gene mutation. In another case, it helped define the pathogenicity of a variant of unknown significance in the SDHB gene. Detection of succinate by (1)H-MRS is a highly specific and sensitive hallmark of SDHx mutations. This noninvasive approach is a simple and robust method allowing in vivo detection of the major biomarker of SDHx-mutated tumors.