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Klin Padiatr 2014; 226(06/07): 309-315
DOI: 10.1055/s-0034-1382021
Review
© Georg Thieme Verlag KG Stuttgart · New York

Neurofibromatosis type 1 (NF1) and Associated Tumors

Neurofibromatose Typ 1 (NF1) und assoziierte Tumoren
T. Rosenbaum
1   Duisburg Wedau Hospital, Department of Pediatrics, Duisburg, Germany
,
K. Wimmer
2   Medical University Innsbruck, Division Human Genetics, Innsbruck, Austria
› Author Affiliations
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Publication History

Publication Date:
25 July 2014 (online)

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Abstract

Neurofibromatosis type 1 (NF1) is a frequent neurocutaneous syndrome that predisposes for various benign and malignant tumors. Most characteristic are neurofibromas which occur in almost all NF1 patients at some point in lifetime. Although neurofibromas are benign tumors they can be disfiguring and plexiform neurofibromas may progress to malignant peripheral nerve sheath tumors. Overall survival rates of patients with these malignant tumors are poor. Other neoplasias frequently observed in NF1 patients are pilocytic astrocytomas, gastrointestinal stromal tumors, pheochromocytomas and juvenile myelomonocytic leukemia. Several other tumors have been reported in NF1 patients but it is unclear if there is a true association between the particular tumor type and NF1. Some of these tumors might be caused by a rare recessively inherited childhood cancer syndrome termed constitutive mismatch repair deficiency syndrome which shows certain phenotypic overlap with NF1 but includes a broad spectrum of tumors which usually do not occur in NF1. The development of NF1-associated tumors is largely explained by the underlying defect of the NF1 gene which results in activation of the RAS proto-oncogene- a key mechanism of tumorigenesis. Several downstream effectors of activated RAS as well as cooperating molecular pathways have been identified. These insights provide the basis to develop novel targeted treatment strategies which are urgently needed to improve the outcome for patients with NF1-associated malignancies.

Zusammenfassung

Die Neurofibromatose Typ 1 (NF1) ist ein häufiges neurokutanes Syndrom und prädisponiert für verschiedene gut- und bösartige Tumoren. Besonders charakteristisch sind Neurofibrome, die bei fast allen Patienten irgendwann im Laufe des Lebens auftreten. Obwohl Neurofibrome gutartige Tumoren darstellen, können sie entstellend sein und plexiforme Neurofibrome können auch zu malignen periphere Nerven­scheidentumoren entarten. Die Überlebensraten von Patienten mit diesen malignen Tumoren sind schlecht. Andere Neoplasien, die oft bei NF1-Patienten auftreten, sind pilozytische Astrozytome, gastrointestinale Stromatumoren, Phäochromozytome und juvenile myelomonozytäre Leukämien. Zahlreiche weitere Tumoren wurden bei NF1-Patienten beschrieben, aber es ist unklar, ob tatsächlich ein Zusammenhang zwischen dem jeweiligen Tumor und der NF1 besteht. ­Einige dieser Tumoren können durch ein seltenes Tumorprädispositions-Syndrom, welches als konstitutives Mismatchreparatur-Defizienz Synd­rom bezeichnet wird, verursacht sein. Dieses Syndrom zeigt phänotypische Überschneidungen mit der NF1, beinhaltet aber ein breites Spektrum an Tumoren, die normalerweise nicht bei NF1 auftreten. Die Entwicklung NF1-assoziierter Tumoren kann durch den zugrundeliegenden Defekt des NF1-Gens erklärt werden, der zu einer Aktivierung des RAS-Proto-Onkogens führt und so einen Schlüsselmechanismus der Tumorgenese in Gang setzt. Zahlreiche Effektoren des aktivierten RAS-Proteins sowie kooperierende molekulare Signalwege wurden identifiziert. Diese Erkenntnisse stellen die Basis dar, auf der neue, gezielte Therapiestra­tegien entwickelt werden können, die dringend benötigt werden, um die Chancen von Patienten mit NF1-assoziierten, malignen Tumoren verbessern.

Key words

neurofibromatosis type 1 - constitutive mismatch repair deficiency syndrome - neurofibroma - optical pathway glioma - juvenile myelomonocytic leukemia

Schlüsselwörter

Neurofibromatose Typ 1 - Konstitutives Mismatchreparatur-Defizienz Syndrom - Neurofibrom - Optikusgliom - juvenile myelomonozytäre Leukämie
 

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