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Bedeutung molekular-zytogenetischer Befunde bei Speicheldrüsentumoren am Beispiel des Mukoepidermoidkarzinoms

Significance of molecular-cytogenetic findings in mucoepidermoid carcinoma as an example of salivary gland tumors

  • Schwerpunkt: Myoepitheliale Tumoren
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Zusammenfassung

Chromosomentranslokationen in Tumoren führen nicht selten zur Ausbildung von Fusionsgenen, die für Proteine mit onkogenen Eigenschaften codieren können. Mukoepidermoidkarzinome sind charakterisiert durch eine Translokation t(11;19), die in 60% der untersuchten Tumoren vorkommt. Diese chromosomale Umlagerung führt zu einem Fusionsgen, das aus dem Exon 1 des MECT 1-Gens und den Exons 2–5 des MAML 2-Gens zusammengesetzt ist. In der Folge bildet sich ein Fusionstranskript, wodurch unabhängig von Notch-Liganden eine Aktivierung der Transkription von HES 1, einem Notch-Zielgen, erfolgt. Durch die veränderte Funktion von MAML 2 kommt es zur Unterbrechung des NOTCH-Signaltransduktionsweges, was einen neuen Mechanismus in der Tumorgenese vermuten lässt. Der Nachweis der Translokation mittels FISH und/oder RT-PCR könnte von erheblichem diagnostischem und möglicherweise auch prognostischem Interesse sein. Zuvor müssen allerdings die molekularen Ereignisse, die einem scheinbar identischen chromosomalen Rearrangement in Warthin-Tumoren zugrunde liegen, geklärt werden. Warthin-Tumoren sind gutartige Speicheldrüsentumoren mit einer vom Mukoepidermoidkarzinom abweichenden Histomorphologie und Histogenese.

Abstract

Chromosome translocations in tumors frequently give rise to fusion genes encoding proteins with oncogenic activities. Mucoepidermoid carcinomas (MEC) are characterized by a t(11;19)(q21–22;p13) translocation found in approximately 60% of the tumors. This t(11;19) translocation results in a fusion gene consisting of exon 1 of the MECT 1 gene and exons 2–5 of the MAML 2 gene. As a result of the t(11;19) a fusion protein is generated which, independent of NOTCH-ligands, activates the transcription of the NOTCH target gene HES 1. The altered function of MAML 2 causes a disruption of NOTCH signalling which suggests a novel mechanism of tumorigenesis. Pending the elucidation of the t(11;19) at the molecular level of an apparently identical chromosomal translocation in Warthin’s tumor, the identification of the translocation in MEC by FISH- and/or RT-PCR-analyses may become important in diagnosis and might have prognostic relevance. Warthin’s tumors are benign salivary gland neoplasms with a distinctive histomorphology and histogenesis completely different from MEC.

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Danksagung

Die Arbeiten wurden durch Zuwendungen der Deutschen Forschungsgemeinschaft (RO 2081/1 und BU 592/5) gefördert.

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Authors and Affiliations

  1. Speicheldrüsenregister, Institut für Oralpathologie, Universitätsklinikum Hamburg-Eppendorf

    K. Röser, K. T. Jäkel &  T. Löning

  2. Zentrum für Humangenetik, Universität Bremen

    J. Bullerdiek

  3. Institut für Oralpathologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg

    T. Löning

Authors
  1. K. Röser
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  2. K. T. Jäkel
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  3. J. Bullerdiek
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  4. T. Löning
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Correspondence to T. Löning.

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Röser, K., Jäkel, K.T., Bullerdiek, J. et al. Bedeutung molekular-zytogenetischer Befunde bei Speicheldrüsentumoren am Beispiel des Mukoepidermoidkarzinoms. Pathologe 26, 359–366 (2005). https://doi.org/10.1007/s00292-005-0778-x

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  • DOI: https://doi.org/10.1007/s00292-005-0778-x

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