Gene Targeting through O-Methylated Catecholamine Metabolite Patterns

Pheochromocytomas and paragangliomas are rare tumors of neuroendocrine tissue that have a prevalence in postmortem studies of approximately 1 in 2000 (1) and an estimated annual incidence of 500–1100 in the US. They may occur within the adrenal medulla or anywhere in the sympathetic chain. Pheochromocytoma has been called the “10% tumor” because approximately 10% occur outside the adrenal medulla, about 10% are bilateral, and 10% are malignant. The clinical features of pheochromocytomas, which are due to the secretion of catecholamines, include episodes of hypertension associated with symptoms such as headache and palpitations, although sustained hypertension may also occur. The main danger is sudden death through hypertensive crises or arrhythmia, either in the community or in the hospital in situations such as surgery. About 90% of cases can be cured. Paragangliomas are more rare than pheochromocytomas and tend to present as space-occupying lesions, with metastases often present at diagnosis. Both types of tumors are associated with conditions that are inherited in an autosomally dominant manner, such as: multiple endocrine neoplasia type 2 (MEN2),2 which is due to a mutation in the RET 3 (ret proto-oncogene) protooncogene; von Hippel–Lindau disease (VHL), which is due to a mutation in the VHL (von Hippel–Lindau tumor suppressor) gene; neurofibromatosis type 1 (NF1), caused by mutation in the NF1 (neurofibromin 1) gene; and mutations in succinate dehydrogenase (SDH) subunits B, C, and D, which are encoded by the SDHB [succinate dehydrogenase complex, subunit B, iron sulfur (Ip)], SDHC (succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa), and SDHD (succinate dehydrogenase complex, subunit D, integral membrane protein) genes. …