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Hereditäres medulläres Schilddrüsenkarzinom

Prädiktive Diagnostik und präventive Maßnahmen

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Der Onkologe Aims and scope

Zusammenfassung

Die Heredität des medullären Schilddrüsenkarzinoms im Rahmen eines MEN2-Syndroms basiert auf heterozygoten Keimbahnmutationen des RET-Protoonkogens. Diese Mutationen sind an sog. Hot Spots des Gens nachzuweisen und stellen damit eine ideale Grundlage für eine molekulargenetische Diagnostik dar, die folglich als Standardmethode in der Diagnostik eines MEN2-Syndroms angesehen wird.

Die molekulargenetische Diagnostik hinsichtlich einer MEN2-assoziierten RET-Keimbahnmutation soll bei allen Patienten mit einer angenommenen sporadischen Form eines MTC oder Phäochromozytoms durchgeführt werden. In die Analyse müssen dabei die Exons 10, 11 und 13–16 einbezogen werden.

Im Ergebnis dieser Untersuchung werden Patienten als sog. Indexpersonen einer neuen MEN2-Familie identifiziert. Der Mutationsnachweis stellt die Grundlage für die prädiktive molekulargenetische Diagnostik innerhalb der betroffenen Familie dar. Diese hat zum Ziel, in jedem Alter Riskopersonen in den Familien auszuschließen oder nachzuweisen. Den Mutationsträgern wird dann die prophylaktische totale Thyreoidektomie als kurative Behandlung angeboten. Die Operation erfolgt entsprechend den Empfehlungen eines risikoadaptierten, allein auf genetischen Daten basierenden Behandlungsregimes. Die Betreuung der betroffenen Familien muss von einer onkologischen sowie humangenetischen Beratung begleitet sein.

Abstract

The heredity of medullary thyroid carcinoma within the MEN2 syndrome is caused by heterozygous germline mutations in the RET proto-oncogene. Since the MEN2-associated mutations involve only hot spots, molecular genetic analysis of the RET proto-oncogene is the perfect tool for diagnosis of MEN2 and is considered the standard method.

Molecular genetic screening for MEN2-associated RET germline mutations should be initiated in all patients with an apparently sporadic medullary thyroid carcinoma or pheochromocytoma. This testing has to include exons 10, 11, and 13–16 of the RET proto-oncogene.

The investigation is aimed at identifying an index person of a new MEN2 family. The detection of such a RET germline mutation is the basis for the predictive molecular genetic testing within the affected family and results in the exclusion or identification of gene carriers. For these persons at risk, prophylactic total thyroidectomy is recommended as a curative procedure according to a risk-adapted genetically based algorithm of treatment. The care of such affected families should be accompanied by oncological and genetic counseling.

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Authors and Affiliations

  1. Universitätsklinikum Carl-Gustav-Carus, Technische Universität Dresden

    G. Fitze

  2. Abt. Chirurgische Forschung, Universitätsklinikum Carl-Gustav-Carus, Technische Universität Dresden

    H. K. Schackert

  3. Klinik für Kinderchirurgie, Universitätsklinikum Carl-Gustav-Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden

    G. Fitze

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Correspondence to G. Fitze.

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Fitze, G., Schackert, H.K. Hereditäres medulläres Schilddrüsenkarzinom. Onkologe 10, 29–37 (2004). https://doi.org/10.1007/s00761-003-0627-6

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