title: The neurofibromatosis type 2 gene is mutated in perineurial cell tumors: a molecular genetic study of eight cases.
abstract: Perineurial cell tumors (PNTs) are rare neoplasms derived from or showing differentiation toward specialized lining cells of the nerve sheath, the perineurial cells. In this study, we have evaluated neurofibromatosis type 2 (NF2) gene alterations in eight PNTs using archival formaldehyde-fixed, paraffin-embedded tissue. Two conventional soft-tissue PNTs from the upper back and chest wall, one retiform soft tissue variant from the scapular region, and five sclerosing PNTs from the fingers and palm were studied. All cases showed histological features of PNTs, and the neoplastic cells were positive for epithelial membrane antigen and negative for S100 protein. The coding sequences (exons 1 to 15) of the NF2 gene were polymerase chain reaction (PCR) amplified and evaluated for mutations by direct sequencing of the PCR products. Five NF2 point mutations, two in the 5'-untranslated region (UTR) and three in exons 3, 6, and 8, were identified in four of eight cases (50%) studied. Exon mutations resulted in changes of predicted amino acids sequences: Asp-->Asn at codon 83, Glu-->Asp at codon 182, and Leu-->Val at codon 241. In two cases (one with a missense mutation in codon 241), the same point mutation in the 5'-UTR at the nucleotide position 8958 was identified. A loss of heterozygosity (LOH) study was performed in three cases. LOH at the NF2 locus was found in one case with a mutation in the 5'-UTR. However, in another case with exon 8 and 5'-UTR mutations, deletion of one allele of the NF2 gene was previously documented by fluorescence in situ hybridization. The coexistence of NF2 gene mutations and LOH at the NF2 locus indicates that the NF2 tumor suppressor gene is altered in PNTs by the two-hit mechanism.
authors: Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, 14th Street and Alaska Ave., Washington, DC 20306-6000, USA. lasota@afip.osd.mil
authors: J
authors: J
authors: Lasota
authors: J F
authors: JF
authors: Fetsch
authors: A
authors: A
authors: Wozniak
authors: B
authors: B
authors: Wasag
authors: R
authors: R
authors: Sciot
authors: M
authors: M
authors: Miettinen
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D005260:Female; D006225:Hand; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation; D020125:Mutation, Missense; D016518:Neurofibromatosis 2 / Q000235:genetics*; D010524:Peripheral Nervous System Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation; D012782:Shoulder; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013899:Thoracic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology