Biallelic inactivation of NF1 in a sporadic plexiform neurofibroma

被引:21
作者
Beert, Eline [1 ]
Brems, Hilde [1 ]
Renard, Marleen [2 ]
Ferreiro, Julio Finalet [1 ]
Melotte, Cindy [1 ]
Thoelen, Reinhilde [1 ]
De Wever, Ivo [3 ]
Sciot, Raf [4 ]
Legius, Eric [1 ]
Debiec-Rychter, Maria [1 ]
机构
[1] Katholieke Univ Leuven, Dept Human Genet, B-3000 Louvain, Belgium
[2] Univ Hosp Leuven, Dept Pediat, Louvain, Belgium
[3] Univ Hosp Leuven, Dept Surg Oncol, Louvain, Belgium
[4] Univ Hosp Leuven, Dept Pathol, Louvain, Belgium
关键词
SEGMENTAL NEUROFIBROMATOSIS; SCHWANN-CELLS; TYPE-1; GENE; TUMORS;
D O I
10.1002/gcc.21969
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Plexiform neurofibromas are a major cause of morbidity in individuals with neurofibromatosis type 1 (NF1). Sporadically, these tumors appear as an isolated feature without other signs of NF1. A role for the NF1 gene in solitary plexiform neurofibromas has never been described. In this study, we report a 13-year-old boy who was diagnosed with a plexiform neurofibroma, without other NF1 diagnostic criteria. The tumor was partially resected and analyzed using different techniques: karyotyping, fluorescence in situ hybridization (FISH), and microarray comparative genomic hybridization (aCGH). Tumor Schwann cell culture and subsequent karyotyping showed a rearrangement involving chromosomes 1 and 17, namely an insertion of chromosomal bands 1p36-35 at 17q11.2. FISH demonstrated that the insertion interrupted the NF1 gene. In addition, a deletion was detected affecting the other NF1 allele. Whole-genome aCGH analysis of the resected tumor confirmed the presence of an 8.28 Mb deletion including the NF1 gene locus in similar to 15-20% of tumor cells. We conclude that biallelic NF1 inactivation was at the origin of the isolated plexiform neurofibroma in this patient. The insertion is most likely the first hit and the large deletion the second hit. (C) 2012 Wiley Periodicals, Inc.
引用
收藏
页码:852 / 857
页数:6
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