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15.10.2018 | Pathologie

Gastrointestinale Stromatumoren

Bedeutung der molekularen Diagnostik für Prognose und Therapie

verfasst von: Priv.-Doz. Dr. Silke Cameron

Erschienen in: Wiener klinisches Magazin | Ausgabe 6/2018

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Zusammenfassung

Hintergrund

Vor 20 Jahren beschrieben Hirota et al. die Expression einer Rezeptortyrosinkinase des Protoonkogens KIT durch einen besonderen Typ mesenchymaler Tumoren des Gastrointestinaltrakts: den gastrointestinalen Stromatumor (GIST). Seither ist die molekulare Diagnostik auch im Hinblick auf therapeutische Möglichkeiten fortgeschritten.

Fragestellung

Dieser Artikel zeichnet die Bedeutung der unterschiedlichen Tyrosinkinase(TK)-Rezeptor-Mutationen sowie die nachgeschalteten Signalwege bis in den Nukleus und ihre Relevanz für die Pathogenese und Therapie der GIST nach.

Material und Methode

Die gängige internationale Literatur wurde strukturiert zur Beantwortung bisher unklarer Fragen zusammengestellt.

Ergebnisse

Während KIT in unterschiedlichen Zellen exprimiert wird (Cajal-Zellen, hämatopoietischen Stammzellen, Melanozyten, Mastzellen und Keimzellen), entstehen GIST aus Cajal-Zellen (oder deren Vorläufern). Somit muß ein definierter zellulärer Kontext für die Entwicklung von GIST bestehen. Mikro-GIST zeigen bereits die Treibermutation im Tyrosinkinaserezeptor, entwickeln sich jedoch erst zu manifesten GIST bei hoher endogener Expression des Transkriptionsfaktors ETV1. Wie KIT- und PDGFRA-Mutationen schließen sich KRAS- und BRAF-Mutationen gegenseitig aus. KRAS- und BRAF-Mutationen können als nachgeschaltete Mutationen vorkommen. Wildtyp(WT)-GIST mit ihren Unterformen der Succinatdehydrogenase(SDH)-Defizienz sind jedoch gesondert zu betrachten. Ob sekundäre Mutationen unter therapeutischem Selektionsdruck neu entstehen oder – bereits vorhanden – selektiert werden, ist bisher unklar. Sekundäre Mutationen scheinen jedoch erst ab einem bestimmten Expressionsniveau Relevanz zu besitzen. Die Therapie fortgeschrittener GIST ist aufgrund der komplexen genomischen Evolution und der Entwicklung von Resistenzen erschwert.

Schlussfolgerungen

Trotz Ihrer Seltenheit bleiben GIST auch für komplexe Therapiesituationen Modelltumoren.

Vorheriger Artikel Medikamentöse Therapie neuroendokriner Neoplasien des Gastrointestinaltrakts

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Titel: Gastrointestinale Stromatumoren
Bedeutung der molekularen Diagnostik für Prognose und Therapie
verfasst von: Priv.-Doz. Dr. Silke Cameron
Publikationsdatum: 15.10.2018
Verlag: Springer Vienna
Erschienen in: Wiener klinisches Magazin / Ausgabe 6/2018
Print ISSN: 1869-1757
Elektronische ISSN: 1613-7817
DOI: https://doi.org/10.1007/s00740-018-0257-7

Springer Medizin Österreich

Zusammenfassung

Hintergrund

Fragestellung

Material und Methode

Ergebnisse

Schlussfolgerungen

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