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New Insights into the Genetics of Familial Chromaffin Cell Tumors
Author(s) -
KOCH CHRISTIAN A.,
VORTMEYER ALEXANDER O.,
ZHUANG ZHENGPING,
BROUWERS FREDERIEKE M.,
PACAK KAREL
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb04409.x
Subject(s) - pheochromocytoma , paraganglioma , sdhd , sdhb , multiple endocrine neoplasia type 2 , germline mutation , biology , multiple endocrine neoplasia , context (archaeology) , germline , neurofibromatosis , genetics , cancer research , carcinogenesis , mutation , endocrinology , pathology , medicine , gene , paleontology
A bstract : We review genetic aspects and recent advances in our understanding of the molecular pathogenesis of familial chromaffin cell tumors (pheochromocytoma, paraganglioma). About 10 percent of pheochromocytomas are familial and occur as part of multiple endocrine neoplasia type 2 (MEN 2), von Hippel‐Lindau (VHL) disease, and neurofibromatosis type 1 (NF 1). A subset of paragangliomas, tumors that can also produce and secrete catecholamines, are also familial and occur in patients with germline mutations in genes that encode subunits of the mitochondrial complex II. The precise molecular mechanisms underlying the pathogenesis of chromaffin cell tumors remain widely unknown, although recent studies in hereditary tumors help elucidate their development. In MEN 2, overrepresentation of mutant RET in selected adrenomedullary cells may be an important mechanism in initiating the formation of a pheochromocytoma. In VHL disease, pheochromocytoma development appears to occur according to Knudson's two‐hit model, a VHL germline mutation and wildtype allelic deletion. Tumorigenesis of NF1‐associated pheochromocytomas remains unknown, as does tumor formation (i.e., carotid body tumor) in patients with germline mutations in SDHB, SDHC , and SDHD , genes that encode subunits of the mitochondrial complex II, the smallest complex in the respiratory chain. Many genetic alterations have been found in sporadic chromaffin cell tumors. However, at present such genetic changes are difficult to place into context with regard to tumor formation and progression.