title: Gains and overexpression identify DEK and E2F3 as targets of chromosome 6p gains in retinoblastoma.
abstract: The paediatric eye tumour retinoblastoma is initiated by inactivation of RB1, a tumour suppressor on chromosome 13q. In addition to RB1 loss, many retinoblastomas show other genetic alterations including gains on chromosomes 6p21-pter and 1q31-q32. Recently, the minimal region of gains on chromosome 6 was narrowed to band p22. We examined genomic gains and expression changes in primary retinoblastomas to identify potential target genes in 6p22. Quantitative multiplex PCR detected copy numbers > or = 3 in 25 (33%) tumours and no gains in 31 of 76 (40%) tumours. The remaining 20 (26%) samples showed gains only at some loci, most often including E2F3 and DEK in 6p22.3. Analysis of RNA from 21 primary retinoblastomas showed that expression levels of these and some other genes in 6p22 correspond to DNA gains. However, KIF 13A, a reported candidate oncogene on 6p, was expressed at low levels or absent. Clinical manifestation of tumours with gains at all 6p22 loci was distinct in that distribution of age at diagnosis was markedly shifted to older age compared to tumours with no or partial gains. In summary, our results suggest that DEK and E2F3 are potential targets of 6p gains in retinoblastoma.
authors: University Children's Hospital of Essen, Universitätsklinikum Essen, D-45122 Essen, Germany.
authors: Corinna
authors: C
authors: Grasemann
authors: Sandrine
authors: S
authors: Gratias
authors: Harald
authors: H
authors: Stephan
authors: Andreas
authors: A
authors: Schüler
authors: Alexander
authors: A
authors: Schramm
authors: Ludger
authors: L
authors: Klein-Hitpass
authors: Harald
authors: H
authors: Rieder
authors: Stephanie
authors: S
authors: Schneider
authors: Ferdinand
authors: F
authors: Kappes
authors: Angelika
authors: A
authors: Eggert
authors: Dietmar R
authors: DR
authors: Lohmann
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6; D017931:DNA Primers; D050699:E2F3 Transcription Factor; D015870:Gene Expression; D006801:Humans; D015513:Oncogene Proteins / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D016133:Polymerase Chain Reaction; D019572:Retinal Neoplasms / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; C084738:DEK protein, human; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D014157:Transcription Factors