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Biallelic inactivation of TP53 rarely contributes to the development of malignant peripheral nerve sheath tumors

Lothe, Ragnhild A.; Smith-Sorensen, Birgitte; Hektoen, Merete; Stenwig, Anna Elisabeth; Mandahl, Nils LU ; Saeter, Gunnar and Mertens, Fredrik LU (2001) In Genes, Chromosomes and Cancer 30(2). p.202-206
Abstract
About 10% of the patients with neurofibromatosis type 1 (NF1) develop malignant peripheral nerve sheath tumors (MPNSTs), accounting for half of all MPNST cases. Several nonrandom chromosomal aberrations have been found, but the target genes remain mostly unrecognized. Mutations in the NF1 and TP53 genes have been found in some MPNSTs, and recent data from mouse models support a synergistic effect of these two genes in the development of MPNST. In the present study, we have analyzed 16 MPNSTs, including 11 from patients with NF1 and 5 sporadic cases, for mutations in the coding sequence of the TP53 gene (exons 2-11). We applied denaturing gradient gel electrophoresis and modifications of this technique for analyses of 12 genomic fragments,... (More)
About 10% of the patients with neurofibromatosis type 1 (NF1) develop malignant peripheral nerve sheath tumors (MPNSTs), accounting for half of all MPNST cases. Several nonrandom chromosomal aberrations have been found, but the target genes remain mostly unrecognized. Mutations in the NF1 and TP53 genes have been found in some MPNSTs, and recent data from mouse models support a synergistic effect of these two genes in the development of MPNST. In the present study, we have analyzed 16 MPNSTs, including 11 from patients with NF1 and 5 sporadic cases, for mutations in the coding sequence of the TP53 gene (exons 2-11). We applied denaturing gradient gel electrophoresis and modifications of this technique for analyses of 12 genomic fragments, followed by direct sequencing for identification of the mutated base(s). None of the MPNSTs revealed mutations. The detection of control mutants for each fragment analyzed, the high sensitivity of the technique, the detection of polymorphisms in some samples, and the high content of tumor tissue in the biopsies imply that false negatives are highly unlikely. Although we cannot exclude that deletions including large parts of the gene remain undetected by the mutation analyses, previous comparative genomic hybridization (CGH), cytogenetic banding analysis, and/or loss of heterozygosity studies on 14 of the cases included here had revealed 17p deletions in only three. We thus conclude that TP53 biallelic inactivation is rare in MPNST, and that the potential impact of an altered TP53 pathway on the malignant transformation of a neurofibroma into an MPNST may more frequently occur by changes in other components of that pathway. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
30
issue
2
pages
202 - 206
publisher
John Wiley & Sons
external identifiers
  • pmid:11135438
  • scopus:0035164154
ISSN
1045-2257
DOI
10.1002/1098-2264(2000)9999:9999<::AID-GCC1079>3.0.CO;2-5
language
English
LU publication?
yes
id
c4bd8834-4e9a-43a4-9475-bfe54ffc567f (old id 1120234)
date added to LUP
2008-07-04 11:59:46
date last changed
2018-05-29 09:27:23
@article{c4bd8834-4e9a-43a4-9475-bfe54ffc567f,
  abstract     = {About 10% of the patients with neurofibromatosis type 1 (NF1) develop malignant peripheral nerve sheath tumors (MPNSTs), accounting for half of all MPNST cases. Several nonrandom chromosomal aberrations have been found, but the target genes remain mostly unrecognized. Mutations in the NF1 and TP53 genes have been found in some MPNSTs, and recent data from mouse models support a synergistic effect of these two genes in the development of MPNST. In the present study, we have analyzed 16 MPNSTs, including 11 from patients with NF1 and 5 sporadic cases, for mutations in the coding sequence of the TP53 gene (exons 2-11). We applied denaturing gradient gel electrophoresis and modifications of this technique for analyses of 12 genomic fragments, followed by direct sequencing for identification of the mutated base(s). None of the MPNSTs revealed mutations. The detection of control mutants for each fragment analyzed, the high sensitivity of the technique, the detection of polymorphisms in some samples, and the high content of tumor tissue in the biopsies imply that false negatives are highly unlikely. Although we cannot exclude that deletions including large parts of the gene remain undetected by the mutation analyses, previous comparative genomic hybridization (CGH), cytogenetic banding analysis, and/or loss of heterozygosity studies on 14 of the cases included here had revealed 17p deletions in only three. We thus conclude that TP53 biallelic inactivation is rare in MPNST, and that the potential impact of an altered TP53 pathway on the malignant transformation of a neurofibroma into an MPNST may more frequently occur by changes in other components of that pathway.},
  author       = {Lothe, Ragnhild A. and Smith-Sorensen, Birgitte and Hektoen, Merete and Stenwig, Anna Elisabeth and Mandahl, Nils and Saeter, Gunnar and Mertens, Fredrik},
  issn         = {1045-2257},
  language     = {eng},
  number       = {2},
  pages        = {202--206},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Biallelic inactivation of TP53 rarely contributes to the development of malignant peripheral nerve sheath tumors},
  url          = {http://dx.doi.org/10.1002/1098-2264(2000)9999:9999<::AID-GCC1079>3.0.CO;2-5},
  volume       = {30},
  year         = {2001},
}