Human Genetics

, Volume 117, Issue 2–3, pp 143–153 | Cite as

A newly identified RET proto-oncogene polymorphism is found in a high number of endocrine tumor patients

  • Wolfgang Gartner
  • Ivelina Mineva
  • Teodora Daneva
  • Sabina Baumgartner-Parzer
  • Bruno Niederle
  • Heinrich Vierhapper
  • Michael Weissel
  • Ludwig WagnerEmail author
Original Investigation


Multiple RET proto-oncogene transcripts, due to genomic variations and alternate splicing, have been described. To investigate endocrine tumor tissue characteristic RET proto-oncogene expression, we performed quantitative RT-PCR, Northern blot and Southern blot analyses of benign and malignant endocrine-derived tissues. We newly describe RET proto-oncogene expression in carcinoid-, gastrinoma- and insulinoma-derived tissue samples. In addition, the presence of a 3′-terminally truncated RET proto-oncogene mRNA variant in benign and malignant thyroid neoplasias, as well as in a pheochromocytoma, an ovarian carcinoma and a medullary thyroid carcinoma, is demonstrated. Southern blot analysis revealed no evidence of gross RET proto-oncogene rearrangements or deletions. As the underlying cause for a bi-allelic TaqI restriction fragment length polymorphism (RFLP), a C (allele 1)/T (allele 2) transition within intron 19, was characterized. This polymorphism is close to a recently described polyadenylation site and lies within a binding site for the nucleic acid binding protein Pbx-1. Screening of healthy subjects and of patients suffering from various endocrine malignancies revealed exclusively allele 1 homozygous and allele 1/allele 2 heterozygous genotypes. Heterozygous genotypes were found in a significantly higher percentage in samples derived from endocrine tumor patients when compared with those from healthy control subjects. Homozygosity for allele 2 was found exclusively in somatic DNA derived from endocrine tumors with high malignant potential. Analysis of DNA derived from varying regions within individual anaplastic thyroid carcinomas revealed an allele 1/allele 2 switch of the RFLP banding pattern, indicating loss of heterozygosity at the RET proto-oncogene locus. In conclusion, our data demonstrate presence of a 5′-terminal RET proto-oncogene transcript in endocrine tissues and reveal a bi-allelic RET proto-oncogene polymorphism. A heterozygous genotype for this polymorphism is found in a considerable number of endocrine tumor patients.


Restriction Fragment Length Polymorphism Medullary Thyroid Carcinoma Endocrine Tumor Anaplastic Thyroid Carcinoma Endocrine Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We want to thank R. Lang and Dr. C. Schwarz for technical support.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Wolfgang Gartner
    • 1
  • Ivelina Mineva
    • 1
  • Teodora Daneva
    • 1
  • Sabina Baumgartner-Parzer
    • 1
  • Bruno Niederle
    • 2
  • Heinrich Vierhapper
    • 1
  • Michael Weissel
    • 1
  • Ludwig Wagner
    • 1
    Email author
  1. 1.Department of Internal Medicine III, General Hospital ViennaVienna Medical UniversityViennaAustria
  2. 2.Department of SurgeryVienna Medical UniversityViennaAustria

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