title: Molecular genetic alterations in adrenal and extra-adrenal pheochromocytomas and paragangliomas.
abstract: Pheochromocytomas and paragangliomas are neuroendocrine neoplasias of neural crest origin. Genetic mutations that are characterized in other human neoplasms are rarely seen in these tumors. About 10% of the patients with pheochromocytomas and paragangliomas present with a family history of von Hippel-Lindau disease (VHL), Multiple endocrine neoplasia type 2 (MEN2), one of the three familial paraganglioma syndromes (PGL; PGL1, PGL3, PGL4), or neurofibromatosis type 1 (NF1). In an even higher percentage, a genetic predisposition is involved in the development of these tumors. The genes of hereditary tumor syndromes such as the aforementioned ones are also ideal to study the molecular pathogenesis in the sporadic counterparts. Many studies have been undertaken to identify important secondary genetic events that contribute to the tumorigenesis of pheochromocytoma or paraganglioma, but a comprehensive review of these data is lacking. Recent findings of CGH and LOH studies provided new starting points to unravel the pathogenesis and progression of these tumors. This review presents an overview of our current understanding of the molecular pathogenesis of pheochromocytoma and paraganglioma.
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus MC Rotterdam, The Netherlands.
authors.forename: Hilde
authors.initials: H
authors.lastname: Dannenberg
authors.forename: Paul
authors.initials: P
authors.lastname: Komminoth
authors.forename: Winand N M
authors.initials: WN
authors.lastname: Dinjens
authors.forename: Ernst Jan M
authors.initials: EJ
authors.lastname: Speel
authors.forename: Ronald R
authors.initials: RR
authors.lastname: de Krijger
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000818:Animals; D014408:Biomarkers, Tumor; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D006623:von Hippel-Lindau Disease / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases