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Aktuelle Urol 2019; 50(01): 84-93
DOI: 10.1055/a-0755-7284
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Molekulargenetische Hochdurchsatzanalysen beim Urothelkarzinom – Möglichkeiten der klinischen Anwendung

High-throughput molecular analysis of urothelial carcinoma: potential clinical applications
Tilman Todenhöfer
1   Universitätsklinikum Tübingen, Dept. of Urology, Tübingen
,
Arkadiusz Miernik
2   Universitätsklinikum Freiburg, Faculty of Medicine, Department of Urology, Freiburg
,
Roland Seiler
3   Department of Urology, University Hospital Bern, Switzerland
› Author Affiliations
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Publication History

Publication Date:
07 February 2019 (online)

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Zusammenfassung

Die Anwendung von Hochdurchsatzanalysen zur Identifizierung von molekularen Veränderungen von Tumorgewebe hat zu einer signifikanten Verbesserung des Verständnisses von der Biologie des Urothelkarzinoms geführt. Unter anderem im Rahmen des Cancer Genome Atlas Projektes (TCGA) konnten anhand Veränderungen des Genexpressionsprofils molekulare Subtypen mit unterschiedlichem biologischem Verhalten identifiziert werden. Das im Rahmen dieser Analysen gewonnene Wissen könnte durch gezielte Anwendungen zu einer deutlichen Veränderung des klinischen Managements von Patienten mit Urothelkarzinomen führen. Erste Daten deuten darauf hin, dass die Bestimmung des molekularen Subtyps für die Entscheidung für oder wider eine neoadjuvante Chemotherapie sinnvoll sein könnte. Weiterhin werden in klinischen Prüfungen aktuell Substanzen untersucht, deren Effekt auf Tumoren mit bestimmten genetischen Veränderungen beschränkt zu sein scheint. Die Identifizierung von bestimmten Mutationen in zirkulierender Tumor-DNA durch liquid biopsies bietet nicht nur die Möglichkeit, metastasierte Tumoren ohne Entnahme einer Gewebebiopsie zu charakterisieren, sondern könnte auch für die Nachsorge von Patienten mit Urothelkarzinom gezielt eingesetzt werden.

Abstract

The application of next-generation high-throughput techniques for the identification of molecular alterations in tumour tissue has greatly improved our knowledge of the biology of urothelial carcinoma. Gene expression analysis performed as part of the Cancer Genome Atlas project (TCGA) enabled the identification of molecular subtypes with distinct biologic features. The knowledge gained through these analyses could lead to a significant change in the clinical management of patients with urothelial carcinoma through targeted applications. Initial studies indicate that the determination of molecular subtypes could inform the decision on whether or not to use neoadjuvant chemotherapy. Moreover, drugs with effects limited to patients with specific genetic alterations are currently under investigation in clinical trials. The identification of specific mutations in circulating tumour DNA (ctDNA) using liquid biopsies enables the characterisation of metastatic tumours without a tissue biopsy. Moreover, circulating tumour DNA could be used in the aftercare of patients with urothelial carcinoma.

Schlüsselwörter

Harnblasenkarzinom - liquid biopsy - molekulare Subtypen - Genomik - personalisierte Therapie

Keywords

Bladder cancer - liquid biopsy - molecular subtypes - genomics - personalised treatment
 

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