Hormones and Cancer

, Volume 3, Issue 4, pp 187–192

Somatic Mutation Analysis of the SDHB, SDHC, SDHD, and RET Genes in the Clinical Assessment of Sporadic and Hereditary Pheochromocytoma

  • Alexander Weber
  • Michael M. Hoffmann
  • Hartmut P. H. Neumann
  • Zoran Erlic
Original Paper

DOI: 10.1007/s12672-012-0113-y

Cite this article as:
Weber, A., Hoffmann, M.M., Neumann, H.P.H. et al. HORM CANC (2012) 3: 187. doi:10.1007/s12672-012-0113-y

Abstract

Systemic analysis of somatic mutations of other susceptibility genes in syndromic tumors as well as apparently sporadic tumors in well-characterized specimens is lacking. Its clinical relevance has not been studied. Our objective was to determine the frequency of second allele inactivation in syndromic tumors and determine the frequency and potential clinical impact of somatic mutations and loss of heterozygosity (LOH) of the known susceptibility genes in syndromic and sporadic tumors. Nine tumor specimens from clinically characterized VHL mutation, five from SDHB mutation, four from SDHD mutation, two from RET mutation carriers, and eight from apparently sporadic cases were analyzed. Tumor DNA mutation screening of the SDHx, VHL, and RET genes and LOH analyses of the SDHx and VHL genes were performed. The Yates-corrected chi-squared test was used for comparison of the clinical data and the molecular-genetic results. Second allele inactivation in tumors was identified in 83 % of VHL, 80 % of SDHB, and 50 % of SDHD specimen. High prevalence of VHL (6/6, p = 0.024) and SDHB (7/7, p = 0.018) somatic mutations has been identified in the sporadic group compared to all others. In the group of the VHL tumors the SDHB somatic events were significantly lower (2/6; p = 0.045). In 18/19 (95 %) of cases, we were able to demonstrate the presence of at least two concomitant affected susceptibility genes. We conclude that LOH is the most prevalent second allele-inactivating event. SDHB and VHL somatic mutation might play a role in the sporadic forms of tumor development. There is no clinical impact of mutation screening or LOH analysis of tumor specimens.

Supplementary material

12672_2012_113_MOESM1_ESM.doc (59 kb)
ESM 1(DOC 59 kb)
12672_2012_113_MOESM2_ESM.doc (58 kb)
ESM 2(DOC 58 kb)

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Alexander Weber
    • 1
  • Michael M. Hoffmann
    • 2
  • Hartmut P. H. Neumann
    • 1
  • Zoran Erlic
    • 1
    • 3
  1. 1.Department of NephrologyUniversity Hospital FreiburgFreiburgGermany
  2. 2.Department of Clinical ChemistryUniversity Hospital FreiburgFreiburgGermany
  3. 3.Department of Internal MedicineUniversity Hospital ZurichZürichSwitzerland

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