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Hereditäre Tumorsyndrome

Kutane Manifestationen und molekulare Pathogenese am Beispiel des Gorlin- und Cowden-Syndroms

Hereditary tumor syndromes

Cutaneous manifestations and molecular pathogenesis of Gorlin and Cowden syndromes

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Zusammenfassung

Eine Reihe von hereditären Tumorsyndromen zeichnet sich durch charakteristische Veränderungen der Haut aus, die wegweisend für eine frühzeitige Diagnosestellung sein können. Beispielhaft werden hier die klinischen Merkmale sowie aktuelle Aspekte der Ätiopathogenese des nävoiden Basalzellkarzinomsyndroms (Gorlin-Syndrom) und des Cowden-Syndroms vorgestellt. Beide Syndrome sind autosomal dominant erblich. Das nävoide Basalzellkarzinomsyndrom ist durch das frühzeitige Auftreten multipler Basalzellkarzinome sowie Fehlbildungen und Tumoren in verschiedenen Organen gekennzeichnet. Ursächlich sind Keimbahnmutationen im PTCH-Tumorsuppressorgen. Das Cowden-Syndrom zeichnet sich durch pathognomonische mukokutane Läsionen sowie ein erhöhtes Risiko für Schilddrüsen-, Mamma- und Endometriumkarzinome aus. Hervorgerufen wird es durch Keimbahnmutationen im PTEN-Tumorsuppressorgen. Die Identifizierung der für hereditäre Tumorsyndrome verantwortlichen Gendefekte und die Entwicklung genetisch manipulierter Mausmodelle haben das Verständnis der molekularen Pathogenese dieser Erkrankungen verbessert und neue Ansätze für eine gezielte, pathogeneseorientierte Therapie aufgezeigt.

Abstract

Several hereditary tumor syndromes are associated with characteristic skin lesions which may facilitate an early diagnosis. We summarize clinical features and recent progress in understanding the etiology and pathogenesis of two selected tumor syndromes, namely nevoid basal cell carcinoma syndrome (Gorlin syndrome) and Cowden syndrome. Both are autosomal dominantly inherited disorders. Nevoid basal cell carcinoma syndrome is characterized by the early onset of multiple basal cell carcinomas as well as developmental defects and a predisposition for other benign and malignant tumors. The syndrome is caused by germline mutations in the PTCH tumor suppressor gene. Cowden syndrome is associated with pathognomonic mucocutaneous lesions, such as facial trichilemmomas, acral keratoses, and mucocutaneous papillomatosis. In addition, Cowden patients are predisposed to carcinomas of the thyroid, breast and endometrium. Cowden syndrome is caused by germline mutations in the PTEN tumor suppressor gene. Identification of the genes causing hereditary tumor syndromes as well as generation of genetically engineered mouse models have greatly advanced our understanding of the molecular pathogenesis of these diseases. Furthermore, novel pathogenesis-based pharmacological strategies are being developed that promise to improve prevention and therapy.

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  1. Hautklinik, Heinrich-Heine-Universität, Düsseldorf

    J. Reifenberger

  2. Hautklinik, Heinrich-Heine-Universität, Moorenstraße 5, 40225 , Düsseldorf

    J. Reifenberger

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Reifenberger, J. Hereditäre Tumorsyndrome. Hautarzt 55, 942–951 (2004). https://doi.org/10.1007/s00105-004-0800-x

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