Differences in allelic distribution of two polymorphisms in the VHL-associated gene CUL2 in pheochromocytoma patients without somatic CUL2 mutations

Eva Maria Duerr, Oliver Gimm, Donna S. Neuberg, Jennifer B. Kum, Steven C. Clifford, Sergio P.A. Toledo, Eamonn R. Maher, Patricia L.M. Dahia, Charis Eng

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Although the two major familial forms of pheochromocytomas, multiple endocrine neoplasia type 2 and von-Hippel-Lindau disease (VHL), have been associated with mutations of the RET and VHL genes, respectively, the molecular pathogenesis of sporadic pheochromocytomas is largely unknown. Recently, a putative tumor suppressor gene has been identified, CUL2, whose product has been shown to interact with the VHL tumor suppressor. To examine whether CUL2 plays a role in pheochromocytoma pathogenesis, we analyzed a series of 26 distinct tumor samples for mutations in the whole coding region of this gene. There were no somatic pathogenic mutations in CUL2, except for 1 sporadic tumor that had a hemizygous gene deletion. We also found 3 novel polymorphisms in the gene. One of these variants, IVS5-6C/T, as well as another previously described one, c.2057G/A, were overrepresented among the pheochromocytoma patients compared to that in a control population (P < 0.005 and P < 0.01, respectively). Although our findings suggest that CUL2 does not play a major role in the pathogenesis of pheochromocytomas, it is still unknown whether epigenetic mechanisms are involved in its inactivation in VHL-associated tumors. Furthermore, the potential role for the overrepresented alleles in the pheochromocytoma group requires further investigation.

Original languageEnglish (US)
Pages (from-to)3207-3211
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume84
Issue number9
DOIs
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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