title: N-MYC amplification, loss of heterozygosity on the short arm of chromosome 1 and DNA ploidy in retinoblastoma.
abstract: Recurrent genetic alterations different from the alteration of the RB1 gene on chromosome 13q14 have been described in retinoblastoma, including structural alterations on the short arm of chromosome 1 and amplification of the N-MYC oncogene. These two genetic alterations are major prognostic factors in neuroblastoma, another embryonic neuro-ectodermal tumour. In order to assess the frequency of these alterations and their possible association with clinical parameters in retinoblastoma, we studied a series of 46 retinoblastoma tumour samples. Ploidy was assessed by flow cytometry, N-MYC copy number was evaluated by a spot-blot procedure using the pNb-1 probe and loss of heterozygosity was investigated by PCR analysis at mini- and microsatellites located on the short arm of chromosome 1. Most tumours were in the diploid or near diploid range; only one case exhibited tetraploidy. N-MYC amplification was observed in only one of the 45 tumours. Loss of heterozygosity on the short arm of chromosome 1 was observed in 9/43 tumours (21%); in particular, its incidence was higher in metastatic than in localised disease (P < 0.05). We suggest that alterations of one or several genes on chromosome 1p might play a role in the oncogenesis or progression of retinoblastoma. Analysis of the long term follow-up of these and additional patients should determine the prognostic value of this parameter.
authors.affiliation: Service de Pédiatrie, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Doz
authors.forename: M
authors.initials: M
authors.lastname: Peter
authors.forename: G
authors.initials: G
authors.lastname: Schleiermacher
authors.forename: P
authors.initials: P
authors.lastname: Vielh
authors.forename: P
authors.initials: P
authors.lastname: Validire
authors.forename: M
authors.initials: M
authors.lastname: Putterman
authors.forename: V
authors.initials: V
authors.lastname: Blanquet
authors.forename: L
authors.initials: L
authors.lastname: Desjardins
authors.forename: J L
authors.initials: JL
authors.lastname: Dufier
authors.forename: J M
authors.initials: JM
authors.lastname: Zucker
authors.forename: V
authors.initials: V
authors.lastname: Mosseri
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: H
authors.initials: H
authors.lastname: Magdelénat
authors.forename: O
authors.initials: O
authors.lastname: Delattre
mesh_terms: D002675:Child, Preschool; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005134:Eye Neoplasms / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D011003:Ploidies; D012175:Retinoblastoma / Q000235:genetics*