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

Bottillo, Irene; Ahiquist, Terje; Brekke, Helge; Danielsen, Stine A.; van den Berg, Eva; Mertens, Fredrik LU ; Lothe, Ragnhild A. and Dallapiccola, Bruno (2009) In Journal of Pathology 217(5). p.693-701
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%)... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
neurofibromatosis, NF1, MPNST, malignant peripheral nerve sheath tumour, MLPA, dHPLC, 1
in
Journal of Pathology
volume
217
issue
5
pages
693 - 701
publisher
John Wiley & Sons
external identifiers
  • wos:000264674900009
  • scopus:64549151639
ISSN
0022-3417
DOI
10.1002/path.2494
language
English
LU publication?
yes
id
6b772f43-b8df-4254-838b-11452a39bee9 (old id 1401454)
date added to LUP
2009-06-15 11:14:48
date last changed
2017-12-10 03:45:05
@article{6b772f43-b8df-4254-838b-11452a39bee9,
  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.},
  author       = {Bottillo, Irene and Ahiquist, Terje and Brekke, Helge and Danielsen, Stine A. and van den Berg, Eva and Mertens, Fredrik and Lothe, Ragnhild A. and Dallapiccola, Bruno},
  issn         = {0022-3417},
  keyword      = {neurofibromatosis,NF1,MPNST,malignant peripheral nerve sheath tumour,MLPA,dHPLC,1},
  language     = {eng},
  number       = {5},
  pages        = {693--701},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Pathology},
  title        = {Germline and somatic NF1 mutations in sporadic and NF1-associated malignant peripheral nerve sheath tumours},
  url          = {http://dx.doi.org/10.1002/path.2494},
  volume       = {217},
  year         = {2009},
}