13 research outputs found
Development and clinical use of a computer assisted decision support system for the interpretation of alkaline phosphatase isoenzyme patterns
Comparison of two commercially available systems for the electrophoretic separation of alkaline phosphatase isoenzymes
Anthropometric and biochemical assessment of the nutritional state in depression: evidence for lower visceral protein plasma levels in depression
Identification of intestinal, intestinal variant, and High-Mr alkaline phosphotase with the resolve-ALP isoelectric focusing system
Immunoradiometric method and electrophoretic system compared for quantifying bone alkaline phosphatase in serum
Germline Mutations in the Mitochondrial 2-Oxoglutarate/Malate Carrier SLC25A11 Gene Confer a Predisposition to Metastatic Paragangliomas
International audienceComprehensive genetic analyses have identified germline SDHB and FH gene mutations as predominant causes of metastatic paraganglioma and pheochromocytoma. However, some suspicious cases remain unexplained. In this study, we performed whole-exome sequencing of a paraganglioma exhibiting an SDHx-like molecular profile in the absence of SDHx or FH mutations and identified a germline mutation in the SLC25A11 gene, which encodes the mitochondrial 2-oxoglutarate/malate carrier. Germline SLC25A11 mutations were identified in six other patients, five of whom had metastatic disease. These mutations were associated with loss of heterozygosity, suggesting that SLC25A11 acts as a tumor-suppressor gene. Pseudohypoxic and hypermethylator phenotypes comparable with those described in SDHx- and FH-related tumors were observed both in tumors with mutated SLC25A11 and in Slc25a11Δ/Δ immortalized mouse chromaffin knockout cells generated by CRISPR-Cas9 technology. These data show that SLC25A11 is a novel paraganglioma susceptibility gene for which loss of function correlates with metastatic presentation