gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Mutational analysis of Smad3, Smad4 and Noggin – The role of TGF-beta/BMP signaling in the pathogenesis of pituitary adenomas

Mutationsanalyse der Gene Smad3, Smad4 und Noggin - Die Rolle des TGF-beta und BMP-Signalweges in der Pathogenese von Hypophysenadenomen

Meeting Abstract

  • corresponding author Jürgen Kreutzer - Neurochirurgische Universitätsklinik der Universität Erlangen, Erlangen
  • D. Gramatzki - Institut für Neuropathologie der Universität Erlangen, Erlangen
  • I. Blümcke - Institut für Neuropathologie der Universität Erlangen, Erlangen
  • R. Fahlbusch - Neurochirurgische Universitätsklinik der Universität Erlangen, Erlangen
  • R. Buslei - Institut für Neuropathologie der Universität Erlangen, Erlangen

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocP 04.38

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0321.shtml

Veröffentlicht: 23. April 2004

© 2004 Kreutzer et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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Objective

The molecular pathogenesis of pituitary adenomas is still poorly understood. One of the few alterations identified up to now are gsp-mutations causing the consecutive activation of the cAMP pathway and the role of the estrogen-induced pituitary tumor-derived transforming gene (PTTG) in prolactinoma tumorigenesis. However, it has recently been found that the bone morphogenetic protein (BMP) inhibitor Noggin, and also the BMP signal cotransducer Smad4 may play a role in the tumorigenesis of pituitary adenomas by modulating the TGF-beta pathway. There has not been, so far, any data on the mutational analysis of these cell cycle regulating genes in human pituitary adenomas in a larger series. Here we present a collaborative research initiative, which fosters the establishment of a tumor bank for molecular-genetical studies on pituitary adenomas, including Smad3, Smad4 and Noggin.

Methods

In a series of 59 patients divided into 8 tumor samples per group (ACTH-, GH-, PRL-, LH/FSH-secreting adenomas; non-secreting adenomas; clinically recurrent adenomas, clinically invasive adenomas and an extra group of 3 Nelson-tumors) and a control group of 50 blood samples, we studied the cell cycle-regulating genes Smad3, Smad4 and Noggin using single-stranded-conformation-polymorphism (SSCP) analysis.

Results

We detected a polymorphism and a point mutation in Exon 8 of the Smad4 gene in two of 8 ACTH-producing pituitary adenomas (20%). With regard to the BMP-inhibitor gene Noggin, we found one point mutation and one polymorphism in a tumor sample of a GH-secreting, as well as in a sample of an invasive non-secreting adenoma (10%). Smad3 analysis revealed polymorphisms in Exon 2 in 10 of 59 tumor samples (17%).

Conclusions

These results suggest that mutational alterations in key genes regulating the BMP and TGF-beta pathway may play a role in the pathogenesis of pituitary adenomas. In the near future, further analysis of a broader spectrum of tumor variants based on our emerging RNA-/DNA-tumor bank will be established to elucidate molecular pathomechanisms in pituitary adenomas with respect to their different growth patterns and endocrinological phenotypes. This will include possible further analysis of genetic instability and other regulative mechanisms of gene expression such as methylation events.