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Novel germline mutation in the transmembrane region of RET gene close to Cys634Ser mutation associated with MEN 2A syndrome

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Abstract

Two mutations on the same allele of RET gene were revealed in a family with predisposition to multiple endocrine neoplasia (MEN) type 2A. The first mutation changes codon 634 from cysteine to serine. The second, a novel mutation in codon 641, changes alanine to serine in the transmembrane domain of the RET protein. Two mutations were present in close proximity in both the patients’ germline and tumor DNA and were absent in DNA isolated from healthy family members and control blood donors. All MEN 2A affected family members suffered from medullary thyroid carcinoma and two of ten patients for pheochromocytoma. No parathyroid gland alterations were observed in patients with two RET gene mutations. Analysis of four genetic polymorphisms in the RET gene showed higher incidence of polymorphisms of exons 11 and 15. The observed allelic imbalance in favor of mutated allele in pheochromocytoma corresponded to higher expression of the RET gene. These observations confirm the multifactorial process leading to development of MEN 2A syndrome.

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Abbreviations

FMTC :

Familial medullary thyroid carcinoma

PCR :

Polymerase chain reaction

MEN :

Multiple endocrine neoplasia

MTC :

Medullary thyroid carcinoma

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Acknowledgements

This work was supported in part by grants from the League Against Cancer of the Slovak Republic, the national program “Use of Cancer Genomics to Improve the Human Population Health,” and the excellence center of the SAS “Molecular Medicine,” and National Institutes of Health (FIRCA TW01217-01). For language corrections and comments we are thankful to Drs. Kathleen Boris-Lawrie and Tiffiney Roberts from the Ohio State University, Columbus, Ohio, USA.

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Authors and Affiliations

  1. Laboratory of Molecular Oncology, Cancer Research Institute SAS, Vlarska 7, 83391, Bratislava, Slovakia

    M. Poturnajova, V. Altanerova & C. Altaner

  2. Second Pediatric Clinic, Children’s University Hospital, Bratislava, Slovakia

    L. Kostalova

  3. Department of Urology, Derer’s University Hospital, Bratislava, Slovakia

    J. Breza

Authors
  1. M. Poturnajova
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  2. V. Altanerova
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  3. L. Kostalova
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  4. J. Breza
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  5. C. Altaner
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Correspondence to C. Altaner.

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Poturnajova, M., Altanerova, V., Kostalova, L. et al. Novel germline mutation in the transmembrane region of RET gene close to Cys634Ser mutation associated with MEN 2A syndrome. J Mol Med 83, 287–295 (2005). https://doi.org/10.1007/s00109-004-0604-6

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  • DOI: https://doi.org/10.1007/s00109-004-0604-6

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