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

• Published in: The journal of clinical endocrinology and metabolism 1999-09, Vol.84 (9), p.3207-3211
• Main Authors: Duerr, Eva-Maria, Gimm, Oliver, Donna S. Neuberg, Kum, Jennifer B, Clifford, Steven C, Toledo, Sergio P. A, Maher, Eamonn R, Dahia, Patricia L. M, Eng, Charis
• Format: Article
• Language: English
• Subjects: Adolescent; Adrenal Gland Neoplasms - genetics; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adult; Alleles; Biological and medical sciences; Carrier Proteins - genetics; Cell Cycle Proteins - genetics; Child; Cullin Proteins; Endocrinopathies; Female; Homozygote; Humans; Loss of Heterozygosity; Male; Medical sciences; Middle Aged; Mutation; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pheochromocytoma - genetics; Polymorphism, Restriction Fragment Length; Polymorphism, Single-Stranded Conformational; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; von Hippel-Lindau Disease - genetics
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.84.9.3207

ABSTRACTAlthough 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.