Premium
A review of the tumour spectrum of germline succinate dehydrogenase gene mutations: Beyond phaeochromocytoma and paraganglioma
Author(s) -
MacFarlane James,
Seong Keat Cheah,
Bisambar Chad,
Madhu Basetti,
Allinson Kieren,
Marker Alison,
Warren Anne,
Park SooMi,
Giger Olivier,
Challis Benjamin G.,
Maher Eamonn R.,
Casey Ruth T.
Publication year - 2020
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.14289
Subject(s) - sdhd , sdhb , sdha , fumarase , paraganglioma , succinate dehydrogenase , citric acid cycle , biology , cancer research , germline mutation , malate dehydrogenase , mutation , biochemistry , gene , enzyme , medicine , pathology
The citric acid cycle, also known as the Krebs cycle, plays an integral role in cellular metabolism and aerobic respiration. Mutations in genes encoding the citric acid cycle enzymes succinate dehydrogenase, fumarate hydratase and malate dehydrogenase all predispose to hereditary tumour syndromes. The succinate dehydrogenase enzyme complex (SDH) couples the oxidation of succinate to fumarate in the citric acid cycle and the reduction of ubiquinone to ubiquinol in the electron transport chain. A loss of function in the succinate dehydrogenase (SDH) enzyme complex is most commonly caused by an inherited mutation in one of the four SDHx genes ( SDHA , SDHB , SDHC and SDHD ). This mechanism was first implicated in familial phaeochromocytoma and paraganglioma. However, over the past two decades the spectrum of tumours associated with SDH deficiency has been extended to include gastrointestinal stromal tumours (GIST), renal cell carcinoma (RCC) and pituitary adenomas. The aim of this review is to describe the extended tumour spectrum associated with SDHx gene mutations and to consider how functional tests may help to establish the role of SDHx mutations in new or unexpected tumour phenotypes.