ITEM METADATA RECORD
Title: Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors
Authors: Beert, Eline
Brems, Hilde
Daniëls, Bruno
De Wever, Ivo
Van Calenbergh, Frank
Schoenaers, Joseph
Debiec-Rychter, Maria
Gevaert, Olivier
De Raedt, Thomas
Van Den Bruel, Annick
de Ravel de l'Argentière, Thomy
Cichowski, Karen
Kluwe, Lan
Mautner, Victor
Sciot, Raf
Legius, Eric # ×
Issue Date: Dec-2011
Publisher: Wiley-Liss, Inc.
Series Title: Genes, Chromosomes & Cancer vol:50 issue:12 pages:1021-1032
Article number: 10.1002/gcc.20921
Abstract: Benign peripheral nerve sheath tumors (PNSTs) are a characteristic feature of neurofibromatosis type I (NF1) patients. NF1 individuals have an 8-13% lifetime risk of developing a malignant PNST (MPNST). Atypical neurofibromas are symptomatic, hypercellular PNSTs, composed of cells with hyperchromatic nuclei in the absence of mitoses. Little is known about the origin and nature of atypical neurofibromas in NF1 patients. In this study, we classified the atypical neurofibromas in the spectrum of NF1-associated PNSTs by analyzing 65 tumor samples from 48 NF1 patients. We compared tumor-specific chromosomal copy number alterations between benign neurofibromas, atypical neurofibromas, and MPNSTs (low-, intermediate-, and high-grade) by karyotyping and microarray-based comparative genome hybridization (aCGH). In 15 benign neurofibromas (4 subcutaneous and 11 plexiform), no copy number alterations were found, except a single event in a plexiform neurofibroma. One highly significant recurrent aberration (15/16) was identified in the atypical neurofibromas, namely a deletion with a minimal overlapping region (MOR) in chromosome band 9p21.3, including CDKN2A and CDKN2B. Copy number loss of the CDKN2A/B gene locus was one of the most common events in the group of MPNSTs, with deletions in low-, intermediate-, and high-grade MPNSTs. In one tumor, we observed a clear transition from a benign-atypical neurofibroma toward an intermediate-grade MPNST, confirmed by both histopathology and aCGH analysis. These data support the hypothesis that atypical neurofibromas are premalignant tumors, with the CDKN2A/B deletion as the first step in the progression toward MPNST. © 2011 Wiley Periodicals, Inc.
ISSN: 1045-2257
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for Neurofibromatosis Research
Division of Crop Biotechnics
Surgical Oncology
Research Group Experimental Neurosurgery and Neuroanatomy
Stomatology & Maxillofacial Surgery Section
Laboratory for Genetics of Malignant Disorders
Translational Cell & Tissue Research
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
beert.pdfpublisher's version pdf Published 1197KbAdobe PDFView/Open Request a copy

These files are only available to some KU Leuven Association staff members

 




All items in Lirias are protected by copyright, with all rights reserved.

© Web of science