title: Novel hereditary forms of pheochromocytomas and paragangliomas.
abstract: Pheochromocytomas and paragangliomas are catecholamine-secreting tumors of neural crest origin that arise from the adrenal medulla or extra-adrenal sympathetic paraganglia, respectively. Over the last decade, the extensive genetic heterogeneity of these tumors came to light with the identification of multiple susceptibility genes. These mutations account for at least one-third of pheochromocytomas and paragangliomas, the highest inheritable proportion of any known human tumor. This chapter will present an overview of genetic and molecular features of the most recently identified hereditary forms of pheochromocytoma and paraganglioma: those caused by mutations in five genes of the succinate dehydrogenase (SDH) complex, the transmembrane-encoding gene TMEM127 and the MYC-binding partner, MAX. Initial genotype-phenotype correlations, as well as emerging functional data, have aligned the new mutants either with defects in hypoxic-angiogenic signaling (SDH-related) or kinase receptor/mTOR pathways (TMEM127 and MAX). These findings, in combination with those of the more well-established syndromes, have been relevant for guiding clinical follow-up. The progress of recent years in understanding the pathogenesis of pheochromocytomas and paragangliomas is expected to continue to improve patient screening and to become, in the long term, the catalyst for development of new therapeutic options for surgically untreatable tumors.
authors: Division of Hematology and Medical Oncology, Department of Medicine, San Antonio, TX 78229, USA. dahia@uthscsa.edu
authors: Patricia L M
authors: PL
authors: Dahia
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics; D013577:Syndrome; D013869:Thiolester Hydrolases / Q000235:genetics
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C499330:MAX protein, human; D013385:Succinate Dehydrogenase; C514740:ACOT13 protein, human; D013869:Thiolester Hydrolases