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Sarkome: Gensignaturen

Sarcoma gene signatures

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Zusammenfassung

Besprochen wird die für Diagnose, Prognose und Prädiktion des Therapieansprechens von Sarkomen wichtigste Gensignatur. Fast die Hälfte aller Sarkome weist eine einfache, spezifische Genläsion auf: rekurrente Translokationen (10–15% der Sarkome), spezifische aktivierende (GIST) bzw. inaktivierende (Rhabdoidtumoren) Mutationen, MDM2-Amplifikation in hoch- und entdifferenzierten Liposarkomen sowie in Intimasarkomen. Vor kurzem wurde eine Genexpressionssignatur veröffentlicht, die sich für die Prädiktion einer Metastasierung deutlich besser eignet als die histologische Graduierung. Sie besteht aus 67 Genen, die alle zu an der chromosomalen Integrität beteiligten Pfaden gehören, was für die besondere Rolle dieser Mechanismen bei der Entstehung von Metastasen spricht. Andererseits gibt es, mit Ausnahme von GIST mit KIT- and PDGFRA-Mutationen, bisher noch keine validierte prädiktive Gensignatur.

Abstract

This review reports the main gene signature specific for the diagnosis, prognosis or prediction of drug response in sarcomas. Almost half of sarcomas show a simple genetic lesion which is specific for the diagnosis: recurrent translocations in 10 to 15% of sarcomas, specific activating and inactivating mutations in GIST and rhabdoid tumor respectively, and MDM2 amplification in well-differentiated and dedifferentiated liposarcomas as well as in intimal sarcoma. A recent study reported a gene expression signature which is much better than histological grading for predicting metastasis outcome. This signature is composed of 67 genes all belonging to pathways involved in chromosome integrity suggesting an important role of these mechanisms in the development of metastases. On the other hand, and except for GIST with KIT and PDGFRA mutations, there is no validated predictive gene signature so far.

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  1. Department of Pathology, Institut Bergonié, Bordeaux Cédex, Frankreich

    F. Chibon &  J.-M. Coindre

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Chibon, F., Coindre, JM. Sarkome: Gensignaturen. Pathologe 32, 32–39 (2011). https://doi.org/10.1007/s00292-010-1393-z

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