Adenom-Karzinom-Sequenz

Schema der Adenom-Karzinom-Sequenz nach Vogelstein

Das Konzept der Adenom-Karzinom-Sequenz besagt, dass die überwiegende Zahl der kolorektalen Karzinome (umgangssprachlich: Darmkrebs) über Stufen genetischer Mutationen aus Adenomen hervorgeht.[1] Als ihr Begründer gilt der amerikanische Arzt Bert Vogelstein.

Bewiesen wurde diese Hypothese erst, nachdem ab 1970 die endoskopische Polypektomie (Entfernung von Polypen) aus allen Abschnitten des Dickdarms möglich wurde.[2] Diese Untersuchungen legten die Grundlage für die Vorsorgekoloskopie ab 2002 in Deutschland.

Molekulargenetisch steht an erster Stelle eine Inaktivierung des APC-Tumorsuppressor-Gens durch Mutation oder Gen-Verlust, gefolgt von einer Mutation des K-Ras-Protoonkogens. Im weiteren Verlauf folgen Mutationen des DCC-Tumorsuppressor-Gens sowie die Inaktivierung des p53-Tumorsuppressorgens.

Literatur

  1. ↑ B. Vogelstein, E. R. Fearon, S. R. Hamilton, S. E. Kern, A. C. Preisinger, M. Leppert, Y. Nakamura, R. White, A. M. Smits, J. L. Bos: Genetic alterations during colorectal-tumor development. In: N Engl J Med. 319(9), 1. Sep 1988, S. 525–532. PMID 2841597
  2. ↑ P. Deyhle: Results of endoscopic polypectomy in the gastrointestinal tract. In: Endoscopy. Suppl. 1980, S. 35–46. PMID 7408789

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