Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors
| Autor: | Thomas De Raedt, Thomy de Ravel, Eric Legius, Karen Cichowski, Eline Beert, Frank Van Calenbergh, L Kluwe, Maria Debiec-Rychter, Olivier Gevaert, Hilde Brems, Victor F. Mautner, Annick Van Den Bruel, Joseph Schoenaers, Raf Sciot, Bruno Daniëls, Ivo De Wever |
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| Přispěvatelé: | Clinical sciences, Medical Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Neurofibromatosis 1 Adolescent DNA Copy Number Variations Neurofibroma/genetics Biology Nerve Sheath Neoplasms Neurofibromatosis 1/genetics Atypical Neurofibroma Comparative Genomic Hybridization/methods Cyclin-Dependent Kinase Inhibitor p16/genetics CDKN2A Plexiform neurofibroma CDKN2B Precancerous Conditions/genetics Genes Neurofibromatosis 1 Genetics medicine Tumor Cells Cultured Neurofibroma Humans risk factors Neurofibromatosis Child neoplasms Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p15 Aged Neurofibromatosis type I Chromosome Aberrations Comparative Genomic Hybridization Karyotyping/methods Karyotype Middle Aged medicine.disease Cyclin-Dependent Kinase Inhibitor p15/genetics Karyotyping young adult Tumor Suppressor Protein p53/genetics Tumor Suppressor Protein p53 mutation Precancerous Conditions Nerve Sheath Neoplasms/genetics |
| Popis: | 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 benignatypical 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. V C 2011 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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