This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Duerr, E.-M. Articles by Eng, C. Search for Related Content PubMed PubMed Citation Articles by Duerr, E.-M. Articles by Eng, C.

Differences in Allelic Distribution of Two Polymorphisms in the VHL-Associated Gene CUL2 in Pheochromocytoma Patients without Somatic CUL2 Mutations¹

Clinical Cancer Genetics and Human Cancer Genetics Programs, Ohio State University Comprehensive Cancer Center (E.-M.D., O.G., J.B.K., P.L.M.D., C.E.), Columbus, Ohio 43210; Dana-Farber Cancer Institute, Harvard Medical School (E.-M.D., D.S.N., J.B.K., P.L.M.D.), Boston, Massachusetts 02115; University of Bonn School of Medicine (E.-M.D.), 53105 Bonn, Germany; the Section of Medical and Molecular Genetics, Department of Pediatrics and Child Health, University of Birmingham School of Medicine (S.C.C., E.R.M.), Birmingham B15 2TG, United Kingdom; the Endocrine Genetics Unit, University of Sao Paulo School of Medicine (S.P.A.T.), Sao Paulo 54199, Brazil; and the Cancer Research Campaign Human Cancer Genetics Research Group, University of Cambridge (C.E.), Cambridge, United Kingdom CB2 2QQ

Address all correspondence and requests for reprints to: Charis Eng, M.D., Ph.D., F.A.C.P., Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, 690C Medical Research Facility, 420 West 12th Avenue, Columbus, Ohio 43210. E-mail: eng-1{at}medctr.osu.edu Or to: Patricia L. M. Dahia, M.D., Ph.D.,

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.

This article has been cited by other articles:

				Y. Maeda, T. Suzuki, X. Pan, G. Chen, S. Pan, T. Bartman, and J. A. Whitsett CUL2 Is Required for the Activity of Hypoxia-inducible Factor and Vasculogenesis J. Biol. Chem., June 6, 2008; 283(23): 16084 - 16092. [Abstract] [Full Text] [PDF]