title: Aberrant CpG island methylation in neurofibromas and neurofibrosarcomas.
abstract: Aberrant methylation of the promoter CpG island of human genes is an alternative gene inactivation mechanism that contributes to the carcinogenesis of human tumours. We have determined the methylation status of the CpG island of 11 tumour-related genes (RB1, p14ARF, p16INK4a, p73, TIMP-3, MGMT, DAPK, THBS1, caspase 8, TP53 and GSTP1) in 18 neurofibromas (including one plexiform neurofibroma) and three neurofibrosarcomas, as well as two non-neoplastic peripheral nerve sheath samples, using methylation-specific polymerase chain reaction. The series included sporadic and neurofibromatosis type 1-associated tumours. The incidence of aberrant methylation in the tumour samples was 52% for THBS1, 43% for MGMT, 33% for TIMP-3, 19% each for p16INK4a and p73, 14% for RB1, 5% for p14ARF, and 0% for DAPK, caspase 8, TP53 and GSTP1. No methylation of these genes was detected in the two samples of non-neoplastic peripheral nerve sheath. All but three samples in the study displayed aberrant methylation in at least one of the studied genes, and there was no correlation between methylation status and the patients' clinical parameters. These findings suggest that methylation of some tumour-related genes may play a significant role in the tumourigenesis of neurofibromas/neurofibrosarcomas.
authors.affiliation: Department of C. Experimental, Laboratorio Oncogenetica Molecular, Hospital Universitario La Paz, 28046 Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Gonzalez-Gomez
authors.forename: M Josefa
authors.initials: MJ
authors.lastname: Bello
authors.forename: Dolores
authors.initials: D
authors.lastname: Arjona
authors.forename: M Eva
authors.initials: ME
authors.lastname: Alonso
authors.forename: Jesus
authors.initials: J
authors.lastname: Lomas
authors.forename: Jose M
authors.initials: JM
authors.lastname: De Campos
authors.forename: M Elena
authors.initials: ME
authors.lastname: Kusak
authors.forename: Manuel
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Jose L
authors.initials: JL
authors.lastname: Sarasa
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rey
mesh_terms: D000328:Adult; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009455:Neurofibroma / Q000235:genetics*; D018319:Neurofibrosarcoma / Q000235:genetics*; D016133:Polymerase Chain Reaction