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Genexpressionsprofile in der onkologischen Diagnostik

Gene expression profiling in cancer diagnostics

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Onkopipeline

Zusammenfassung

Tumorerkrankungen stellen in Deutschland nach wie vor die zweithäufigste Tordesursache dar. Neben der Entwicklung wirksamer primärer und sekundärer Präventionsmaßnahmen sind vor allem Methoden zur Verbesserung der Diagnose und Subklassifikation sowie zur Prognoseeinschätzung der einzelnen Tumorentitäten dazu geeignet, die krebsbedingte Letalität langfristig zu senken. Die klassische Diagnose eines Tumors stützt sich vielfach auf seine histomorphologische Charakterisierung, wohingegen die prognostische Einschätzung zusätzlich durch das Stadium der Erkrankung bei Diagnose bestimmt wird. Nach der Etablierung von Hochdurchsatzmethoden zur Erstellung von Genexpressionsprofilen von Tumorbiopsien wurde im vergangenen Jahrzehnt untersucht, ob die molekulare Charakterisierung von Tumoren die diagnostische Sicherheit zusätzlich erhöhen und die Einschätzung der Prognose verbessern kann. Hierzu wurden vor allem Studien beim Mamma-, Lungen- und Kolonkarzinom durchgeführt mit dem Ziel, in der adjuvanten Situation bei Vorliegen eines frühen Stadiums feststellen zu können, welche Patientenkollektive tatsächlich von einer Chemotherapie profitieren würden. Ferner wurden Genexpressionsprofile dazu genutzt, Tumoren mit unklarem Primarius ihrem Ursprungsgewebe zuzuordnen. Darüber hinaus wurde mittels Genexpressionsanalyse eine ergänzende molekulare Klassifikation sowohl von B-Zell-Non-Hodgkin-Lymphomen als auch von lymphatischen und myeloischen Leukämien ermöglicht, wodurch möglicherweise sowohl die Diagnostik als auch die Einschätzung der Prognose dieser Erkrankungen langfristig verbessert werden können. Obwohl mittlerweile zahlreiche Signaturen und Prädiktoren zu einzelnen Neoplasien veröffentlicht wurden, fand in Deutschland bisher keiner der Tests Eingang in die leitlinienbasierte Diagnostik und Therapie einer malignen Erkrankung. Dies ist vor allem darauf zurückzuführen, dass die vielversprechenden Ergebnisse zunächst in großen prospektiven klinischen Studien evaluiert werden müssen. Erst nach Abschluss dieser Studien wird zu entscheiden sein, ob und welche Testverfahren tatsächlich geeignet sind, den Verlauf einer bestimmten Tumorerkrankung signifikant zu verbessern.

Abstract

Cancer still represents the second leading cause of death in Germany. Besides the strengthening of primary and secondary tumor prevention, also the improvement of diagnosis, subclassification and assessment of prognosis will be necessary for lowering the mortality of certain tumor entities. Cancer diagnosis is often based on histological characterization of tumor biopsy material, while the stage of disease strongly influences the prognosis of an individual patient. With the development of high-throughput technologies to perform gene expression profiling during the last decade, multiple clinical trials assessed the value of gene expression profiling for molecular characterization of cancer as well as its impact on diagnosis and prognosis of disease. Mainly in breast, lung, and colon cancer, gene expression profiling was performed to investigate which patients in early-stage disease might benefit from adjuvant chemotherapy after complete tumor resection. Gene expression profiling was also used to determine the primary tissue of cancer of unknown primary. Moreover, gene expression profiling was performed to further classify B cell non-Hodgkin’s lymphoma and also leukemia in order to improve diagnosis as well as the therapeutic options due to the development of novel prognostic markers. Although numerous tumor-specific signatures and prognostic predictors were established in these studies, none has been implemented in the German guideline-based therapeutic decision tree for any of these tumor entities. This is mainly due to the lack of appropriate validation trials, which are urgently needed to introduce this promising technology into routine clinical practice to improve diagnosis and prognosis of cancer.

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  1. Genomics and Immunoregulation, LIMES (Life and Medical Sciences Bonn) Institut, Universität Bonn, Bonn, Germany

    Andrea Staratschek-Jox

  2. Program Unit, Molecular Immune & Cell Biology, Genomics and Immunoregulation, LIMES (Life and Medical Sciences Bonn) Institut, Rheinische Friedrich-Wilhelms-Universität Bonn, Karlrobert-Kreiten-Straße 13, 53115, Bonn, Germany

    Andrea Staratschek-Jox

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Gaarz, A., Debey-Pascher, S., Classen, S. et al. Genexpressionsprofile in der onkologischen Diagnostik. Onkopipeline 2, 44–52 (2009). https://doi.org/10.1007/s15035-009-0150-3

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