title: Genome instability in secondary solid tumors developing after radiotherapy of bilateral retinoblastoma.
abstract: Genome alterations of seven secondary tumors (five osteosarcomas, one malignant peripheral sheath nerve tumor, one leiomyosarcoma) occurring in the field of irradiation of patients treated for bilateral retinoblastoma have been studied. These patients were predisposed to develop radiation-induced tumors because of the presence of a germ line mutation in the retinoblastoma gene (RB1). Tumor cells were characterized by a high chromosome instability whereas microsatellites and minisatellites were found to be stable. In all tumors, the normal RB1 allele was lost with the corresponding chromosome 13, whereas the germ line mutated allele was retained. The two alleles of TP53 were inactivated, one by deletion of the short arm of chromosome 17, the other by mutation. As compared with non-radiation-induced tumors, the observed panel of TP53 mutations was uncommon with sites not recurrently found otherwise and a high rate of deletions (3/7). In these predisposed patients, the loss of the single normal allele of RB1 is rather due to the radiation-induced chromosome instability than a direct effect of ionizing radiation.
authors.affiliation: Institut Curie - CNRS UMR 147, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: S H
authors.initials: SH
authors.lastname: Lefèvre
authors.forename: N
authors.initials: N
authors.lastname: Vogt
authors.forename: A M
authors.initials: AM
authors.lastname: Dutrillaux
authors.forename: L
authors.initials: L
authors.lastname: Chauveinc
authors.forename: D
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: F
authors.initials: F
authors.lastname: Doz
authors.forename: L
authors.initials: L
authors.lastname: Desjardins
authors.forename: B
authors.initials: B
authors.lastname: Dutrillaux
authors.forename: S
authors.initials: S
authors.lastname: Chevillard
authors.forename: B
authors.initials: B
authors.lastname: Malfoy
mesh_terms: D020732:Cytogenetic Analysis; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D018598:Minisatellite Repeats; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D011839:Radiation, Ionizing; D012175:Retinoblastoma / Q000532:radiotherapy*