RESUMO
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.
Assuntos
RNA Helicases DEAD-box/genética , Amplificação de Genes , Neuroblastoma/genética , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , RNA Neoplásico/genética , Dosagem de Genes , Humanos , Hibridização in Situ Fluorescente , Proteína Proto-Oncogênica N-Myc , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
BACKGROUND: Information on the incidence of infectious complications during for treatment for high risk neuroblastoma (HR-NB) is limited. Bacteremias and invasive mycoses may be considered surrogate markers of the infection burden. PATIENTS AND METHODS: Data on bacteremias and invasive mycoses occurring during 3 consecutive protocols for front line (NB-89; NB-92; NB-97) or salvage therapy (TVD) for HR-NB were reviewed. The cumulative risk of developing a first episode and the rate of infections during the entire length of each protocol were evaluated. RESULTS: Front line protocols were given to 80 patients for a total of 22,070 days at risk; salvage treatment was given to 24 children for 2,909 days at risk. During front line therapy 41 infectious episodes were diagnosed in 29 (36%) patients, for a 45% cumulative risk and an infection rate (IR) of 0.19/100 patient-days-at risk. Salvage therapy determined five infectious episodes in four (17%) patients, with a 39% cumulative risk, and an IR of 0.17. The IR during the phase of high dose chemotherapy with hematopoietic stem cell rescue (megatherapy) included in the three front line protocols decreased over time (1.54 in NB-89; 0.52 in NB-92 and 0.0 in NB 97; P = 0.001), possibly because of the use of less aggressive conditioning regimens, without radiotherapy. CONCLUSIONS: The IRs of protocols for HR-NB did not change over time. The megatherapy-related phases are those at highest risk.