Losses in chromosomes 17, 19, and 22q in neurofibromatosis type 1 and sporadic neurofibromas

Abstract

Neurofibromatosis type 1 (von Recklinghausen's NF1) is an autosomal dominant disease associated with an increased risk of benign and malignant neoplasia including malignant peripheral nerve sheath tumors (MPNSTs). In this study, we employed comparative genomic hybridization (CGH) to determine changes in the relative chromosome copy number in 24 patients with neurofibromas, including 12 NF1-associated and 12 sporadic cases. Differences in the frequency and distribution of chromosomal imbalances were observed in both NF1-asociated and sporadic neurofibromas. Chromosomal imbalances were more common in NF1-associated tumors than in sporadic neurofibromas. In both groups, the number of losses was higher than the number of gains, suggesting a predominant role of tumor suppressor gene in tumorigenesis. A number of new chromosomal imbalances were noted including chromosomes 17, 19, and chromosome arm 22q, which may be related to oncogenes or tumor suppressor genes in neurofibromas. In NF1-associated neurofibromas, the most frequent losses were found in chromosome 17 (the minimal common regions were 17p11.2-->p13 in nine cases and 17q24-->q25 in six cases) and 19p (19p13.2 in nine cases). In addition, both NF1-associated and sporadic neurofibromas often exhibited losses at chromosome arms 19q and 22q (in NF1 tumors, the minimal common regions were 19q13.2-->qter in seven cases).