Perspektiven der Molekular-/Gendiagnostik in der Gastroenterologie am Beispiel des vererbbaren kolorektalen Karzinoms

Zusammenfassung

Die molekularen Grundlagen des vererbbaren kolorektalen Karzinoms wurden in den letzten 10 Jahren intensiv erforscht. Keimbahnmutationen einer Reihe von Genen sind für das hereditäre nicht-Polyposis-assoziierte kolorektale Karzinom (HNPCC) und die familiäre adenomatöse Polyposis coli (FAP) verantwortlich. Diese Kenntnisse ermöglichen eine prädiktive molekulare Diagnostik, die Konsequenzen für präventive Strategien einschließlich spezieller Vorsorgemaßnahmen und präventiver chirurgischer Behandlung hat. Von besonderer Bedeutung ist der Nachweis des Nichtvorliegens der familieneigenen Mutation, der es erlaubt, entsprechende Familienangehörige aus dem Vorsorgeprogramm zu entlassen. Jedoch bleiben weiterhin zahlreiche Fragen bezüglich der Genotyp/Phänotyp Korrelation wie z. B. im Zusammenhang mit der Penetranz der Erkrankung, der Organmanifestation der Tumoren und dem Zeitpunkt der Erkrankung offen. Die Anwendung der molekulargenetischen Kenntnisse in der klinischen Praxis ist deshalb eine große Herausforderung für Grundlagenforscher und Kliniker.

Abstract

The knowledge on the molecular basis of inherited colorectal cancers has been progressively increasing, and it is well established now that germline mutations of several genes contribute to hereditary nonpolyposis colorectal cancer syndrome (HNPCC) and familial adenomatous polyposis (FAP). Additionaly, predictive molecular diagnostics impacts on the prevention of these diseases, including regular colonoscopies and preventive surgical treatment, while allowing the exclusion of non-carriers of the pathogenic mutation from surveillance programs. However, there are still several questions concerning genotype/phenotype correlation, such as disease penetrance, organ distribution of the malignant disease and time of onset of the disease, which may only begin to be answered through the integration of the results of basic molecular research with the clinical practice.

Schlüsselwörter

Familiäre adenomatöse Polyposis - Hereditäres nicht-Polyposis-assoziiertes kolorektales Karzinom - molekulare Diagnostik - klinische Konsequenzen

Key words

Familial adenomatous polyposis - hereditary nonpolyposis colorectal cancer syndrome - molecular diagnostics - clinical consequences

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