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

Irene Bottillo, Terje Ahlquist, Helge Brekke, Stine A. Danielsen, Eva Den Van Berg, Fredrik Mertens, Ragnhild A. Lothe, Bruno Dallapiccola

Research output: Contribution to journalArticlepeer-review


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 NFI mutations, the information on somatic mutations in MPNSTs is limited. In this study, we screened NFI, 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 NFI mutations were detected in ten NF1 patients, including three frameshift, three nonsense, one missense, one splicing alteration, and two large deletions. Somatic NFI 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 NFI mutation. A major role of the KRAS and BRAF genes was ruled out. The spectrum of germline NFI 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.

Original languageEnglish
Pages (from-to)693-701
Number of pages9
JournalJournal of Pathology
Issue number5
Publication statusPublished - Apr 2009


  • Malignant peripheral nerve sheath tumour
  • MLPA
  • Neurofibromatosis 1
  • NF1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)


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