title: Concomitant DDX1 and MYCN gain in neuroblastoma.
abstract: DDX1, a gene mapping to the 2p24 region, has been observed to be co-amplified with MYCN in neuroblastoma. Co-amplification of the DDX1 gene is a consequence of the short physical distance between the two genes. Recently, it has been found that neuroblastoma cells can show a low increase in MYCN gene copy number, defined as MYCN gain. We studied 13 neuroblastomas with MYCN gain to evaluate the status of the DDX1 gene. We investigated DDX1/MYCN gain by double-colour FISH on interphase nuclei. All cases showed concomitant low extra copy number of DDX1 and MYCN. Heterogeneous distribution of nuclei displaying DDX1/MYCN gain was observed in almost all tumours, suggesting a clonal evolution of cells with DDX1/MYCN gain. This is the first report that shows DDX1 co-gained with MYCN in neuroblastoma and indicates that DDX1 over-representation is closely associated with an increase in MYCN copy number in neuroblastoma cells. Since DDX1 has already been found co-amplified with MYCN, DDX1 gain seems to be a further rearrangement due to the physical proximity of the two genes. Moreover, all patients with DDX1/MYCN gain show a good overall survival but a high frequency of adverse events.
authors.affiliation: Laboratory of Neuroblastoma Research, Italian Neuroblastoma Foundation, National Institute for Cancer Research (IST), Largo R. Benzi 10, 16132 Genoa, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Defferrari
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Tonini
authors.forename: Massimo
authors.initials: M
authors.lastname: Conte
authors.forename: Filippo
authors.initials: F
authors.lastname: Papio
authors.forename: Angela Rita
authors.initials: AR
authors.lastname: Sementa
authors.forename: Alexander
authors.initials: A
authors.lastname: Valent
authors.forename: Francesca
authors.initials: F
authors.lastname: Schena
authors.forename: Patrizia
authors.initials: P
authors.lastname: Perri
authors.forename: Katia
authors.initials: K
authors.lastname: Mazzocco
mesh_terms: D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C086252:DDX1 protein, human; D053487:DEAD-box RNA Helicases