Germline and somatic NF1 mutations in sporadic and NF1-associated malignant peripheral nerve sheath tumours

Irene Bottillo, Terje Ahiquist, Helge Brekke, Stine A. Danielsen, Eva van den Berg, Fredrik Mertens, Ragnhild A. Lothe, Bruno Dallapiccola*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    91 Citations (Scopus)

    Abstract

    Malignant peripheral nerve sheath tumours (MPNSTs) are a malignancy occurring with increased frequency in patients with neurofibromatosis type 1 (NF1). In contrast to the well-known spectrum of germline NF1 mutations, the information on somatic mutations in MPNSTs is limited. In this study, we screened NF1, KRAS, and BRAF in 47 MPNSTs from patients with (n = 25) and without (n = 22) NF1. In addition, DNA from peripheral blood and cutaneous neurofibroma biopsies from, respectively, 14/25 and 7/25 of the NF1 patients were analysed. Germline NF1 mutations were detected in ten NF1 patients, including three frameshift, three nonsense, one missense, one splicing alteration, and two large deletions. Somatic NF1 mutations were found in 10/25 (40%) NF1-associated MPNSTs, in 3/7 (43%) neurofibromas, and in 9/22 (41%) sporadic MPNSTs. Large genomic copy number changes accounted for 6/10 and 7/13 somatic mutations in NF1-associated and sporadic MPNSTs, respectively. Two NF1-associated and 13 sporadic MPNSTs did not show any NF1 mutation. A major role of the KRAS and BRAF genes was ruled out. The spectrum of germline NF1 mutations in neurofibromatosis patients with MPNST is different from the spectrum of somatic mutations seen in MPNSTs. However, the somatic events share common characteristics with the NF1-related and the sporadic tumours. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

    Original languageEnglish
    Pages (from-to)693-701
    Number of pages9
    JournalJOURNAL OF PATHOLOGY
    Volume217
    Issue number5
    DOIs
    Publication statusPublished - Apr-2009

    Keywords

    • MPNST
    • malignant peripheral nerve sheath tumour
    • NF1
    • neurofibromatosis 1
    • dHPLC
    • MLPA
    • NEUROFIBROMATOSIS TYPE-1 NF1
    • MICRODELETION PATIENTS
    • BENIGN NEUROFIBROMAS
    • MESSENGER-RNA
    • GENE
    • RECOMBINATION
    • INACTIVATION
    • SPECTRUM
    • DELETIONS
    • SEQUENCE

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