Endocrine Abstracts

Tumorigenesis and intermediary metabolism have a long common history. Eighty years ago, the biochemist Otto Warburg pioneered a large field of researches devoted to the metabolism of tumour cells. He reported a spectacular shift from a normal aerobic metabolism to a highly glycolytic metabolism, associated with a low respiration rate, despite aerobic conditions. After being forgotten for decades, a renewed interest in the Warburg effect has resulted from the report that, mitoc...

SDHA, B, C, and D (SDHx) genes encode the four subunits of succinate dehydrogenase (SDH), a mitochondrial enzyme of the tricarboxylic acid (TCA) cycle that oxidizes succinate into fumarate. They were the first genes encoding a mitochondrial enzyme demonstrated to act as tumor suppressors, an important finding supporting the hypothesis of a direct link between mitochondrial dysfunction and cancer proposed by Otto Warburg in the 1920’s. It is estimated that germline mutatio...

Since the discovery of mutations in succinate dehydrogenase (SDH) complex early this century, it has been shown that tumours underpinned by deficiencies in this metabolic enzyme will demonstrate altered cell metabolism. However, the precise nature of these changes remains poorly described. The metabolic network within cells is highly redundant, with multiple pathways capable of synthesising the required building blocks for cell growth. By the very fact that SDH-deficient cells...

Since the discovery of mutations in succinate dehydrogenase (SDH) complex early this century, it has been shown that tumours underpinned by deficiencies in this metabolic enzyme will demonstrate altered cell metabolism. However, the precise nature of these changes remains poorly described. The metabolic network within cells is highly redundant, with multiple pathways capable of synthesising the required building blocks for cell growth. By the very fact that SDH-deficient cells...

Integrative genomics studies of paragangliomas (PGL) have shown that PGL susceptibility genes are the main drivers of tumorigenesis. Comprehensive genetic analyses have identified germline SDHB and, to a lesser extent, FH gene mutations, as predominant causes of metastatic PGL. However, some suspicious cases remain unexplained. We performed whole-exome sequencing of a paraganglioma exhibiting an SDHx-like molecular profile in the absence of SDHx<...

Context: Paragangliomas and pheochromocytomas (PPGL) are rare neuroendocrine tumors, characterized by a strong genetic component. Indeed, up to 40% of patients carry a germline mutation in a PPGL susceptibility gene. In accordance with the international recommendations, genotyping of PPGL susceptibility genes is therefore proposed to all patients with PPGL, but it has actually never been shown whether the identification of a germline mutation in one PPGL susceptibility gene ch...