Our results indicate that DDX1 coamplification correlates with a better prognosis and improved patient survival in MYCN-amplified neurobastoma.
could not be confirmed in our data set (63 patients: event free survival, P ϭ .84; overall survival, P ϭ .97, log-rank test).Summarizing, our data indicate that-in contrast to the observations by Weber et al-DDX1 coamplification has no significant prognostic (adverse or beneficial) value in MYCN amplified tumors. Furthermore, our own data, previous studies, 3 and the observations by Weber et al show that the gene coamplification frequency within the MYCN amplicon correlates with the physical distance to MYCN. Hence, these findings strongly suggest that the process of coamplification occurs coincidentally, and is not subject to selection, further supporting our conclusions. Further arguments against a beneficial effect of DDX1 coamplification come from published reports attributing oncogenic characteristics to DDX1. 3 In conclusion, the absence of significant prognostic power of DDX1 coamplification after re-evaluation of a large series of MYCN-amplified tumors from patients with long follow-up times, the marginally significant P values obtained in Weber et al (0.027 and 0.01), the physical association between gene coamplification and distance to the core target of amplification, and the oncogenic properties of DDX1 strongly suggest that the observations made by Weber et al constitute at the best a marginal effect. Other large cohorts of uniformly treated neuroblastoma tumors need to be studied to clarify these discrepant findings and to demonstrate whether DDX1 coamplification has any favorable predictive power. The question remains though how such an effect would be translated to the clinic in order to achieve an improved outcome for both patient groups.
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