New insights into the genetics of familial chromaffin cell tumors

Christian A. Koch, Alexander Vortmeyer, Zhengping Zhuang, Frederieke M. Brouwers, Karel Pacak

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11-28
Number of pages18
JournalAnnals of the New York Academy of Sciences
Volume970
DOIs
StatePublished - Jun 5 2002
Externally publishedYes

Fingerprint

Chromaffin Cells
Tumors
Pheochromocytoma
Germ-Line Mutation
Neoplasms
Multiple Endocrine Neoplasia Type 2a
von Hippel-Lindau Disease
Paraganglioma
Carotid Body Tumor
Genes
Neurofibromatosis 1
Electron Transport
Genetics
Familial
Cells
Catecholamines
Carcinogenesis
Mutation
Gene

Keywords

  • Multiple endocrine neoplasia type 2
  • NF1
  • Paraganglioma
  • Pheochromocytoma
  • RET
  • SDHB
  • SDHC
  • SDHD
  • Second hit
  • Tumor formation
  • VHL

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

New insights into the genetics of familial chromaffin cell tumors. / Koch, Christian A.; Vortmeyer, Alexander; Zhuang, Zhengping; Brouwers, Frederieke M.; Pacak, Karel.

In: Annals of the New York Academy of Sciences, Vol. 970, 05.06.2002, p. 11-28.

Research output: Contribution to journalArticle

Koch, Christian A. ; Vortmeyer, Alexander ; Zhuang, Zhengping ; Brouwers, Frederieke M. ; Pacak, Karel. / New insights into the genetics of familial chromaffin cell tumors. In: Annals of the New York Academy of Sciences. 2002 ; Vol. 970. pp. 11-28.
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