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 journalArticle

11 Citations (Scopus)

Abstract

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

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von Hippel-Lindau Disease
Pheochromocytoma
Polymorphism
Tumors
Genes
Mutation
Neoplasms
Multiple Endocrine Neoplasia Type 2a
Gene Deletion
Tumor Suppressor Genes
Epigenomics
Alleles
Population

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Differences in allelic distribution of two polymorphisms in the VHL-associated gene CUL2 in pheochromocytoma patients without somatic CUL2 mutations. / Duerr, Eva Maria; Gimm, Oliver; Neuberg, Donna S.; Kum, Jennifer B.; Clifford, Steven C.; Toledo, Sergio P A; Maher, Eamonn R.; Dahia, Patricia L M; Eng, Charis.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 84, No. 9, 1999, p. 3207-3211.

Research output: Contribution to journalArticle

Duerr, Eva Maria ; Gimm, Oliver ; Neuberg, Donna S. ; Kum, Jennifer B. ; Clifford, Steven C. ; Toledo, Sergio P A ; Maher, Eamonn R. ; Dahia, Patricia L M ; Eng, Charis. / Differences in allelic distribution of two polymorphisms in the VHL-associated gene CUL2 in pheochromocytoma patients without somatic CUL2 mutations. In: Journal of Clinical Endocrinology and Metabolism. 1999 ; Vol. 84, No. 9. pp. 3207-3211.
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title = "Differences in allelic distribution of two polymorphisms in the VHL-associated gene CUL2 in pheochromocytoma patients without somatic CUL2 mutations",
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.",
author = "Duerr, {Eva Maria} and Oliver Gimm and Neuberg, {Donna S.} and Kum, {Jennifer B.} and Clifford, {Steven C.} and Toledo, {Sergio P A} and Maher, {Eamonn R.} and Dahia, {Patricia L M} and Charis Eng",
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T1 - Differences in allelic distribution of two polymorphisms in the VHL-associated gene CUL2 in pheochromocytoma patients without somatic CUL2 mutations

AU - Duerr, Eva Maria

AU - Gimm, Oliver

AU - Neuberg, Donna S.

AU - Kum, Jennifer B.

AU - Clifford, Steven C.

AU - Toledo, Sergio P A

AU - Maher, Eamonn R.

AU - Dahia, Patricia L M

AU - Eng, Charis

PY - 1999

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N2 - 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.

AB - 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.

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