Germinal mutations of RET, SDHB, SDHD, and VHL genes in patients with apparently sporadic pheochromocytomas and paragangliomas

Endokrynol Pol. 2010 Jan-Feb;61(1):43-8.

Abstract

Introduction: Pheochromocytomas and paragangliomas are derived from neural crest cells and are localized mainly in adrenal medulla and sympathetic or parasympathetic ganglia. They can be inherited (25%) and be part of multi-endocrine syndromes such as MEN2 syndrome, von Hippel-Lindau syndrome, pheochromocytoma/paraganglioma syndrome, neurofibromatosis type 1, and Sturge-Weber syndrome. Clinical presentation can sometimes be atypical and does not always allow proper diagnosis. In such situations, DNA analysis can be helpful, especially when the pheochromocytoma is the first and only symptom.

Material and methods: We analyzed DNA from 60 patients diagnosed and treated in the Centre of Oncology with a diagnosis of pheochromocytoma or paraganglioma. DNA analysis was carried out for RET (exons 10, 11, 13, and 16), SDHB, SDHD, and VHL genes. Techniques used for the analysis were direct sequence analysis, MSSCP, and RFLP.

Results: Germinal mutations were found in 16 patients (26,7%). Most frequent were mutations in RET proto-oncogene, followed by VHL gene, one mutation in SDHB, and one in SDHD genes. A comparison of some of the clinical features of both groups (with and without mutation) showed statistically significant differences.

Conclusions: The results of our study show that genetic predisposition is frequent in chromaffin tissue tumours, which indicates that DNA analysis is necessary in every case, also because of possible atypical clinical presentation. (Pol J Endocrinol 2010; 61 (1): 43-48).

MeSH terms

  • Adolescent
  • Adrenal Gland Neoplasms / genetics*
  • Adult
  • Child
  • Germ-Line Mutation*
  • Humans
  • Middle Aged
  • Neoplasms, Multiple Primary / genetics
  • Paraganglioma / genetics*
  • Pheochromocytoma / genetics*
  • Pheochromocytoma / secondary
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-ret / genetics*
  • Succinate Dehydrogenase / genetics*
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics*
  • Young Adult

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • SDHD protein, human
  • SDHB protein, human
  • Succinate Dehydrogenase
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • VHL protein, human