DDX4 and Neuroblastoma: Limited Evidence for Association

A genome‑wide association study identified a potential link between DDX4 (HGNC:18700) and neuroblastoma (MONDO_0005072) in low‑risk patients (PMID:21436895). In this study, statistical analyses revealed significant SNP associations for DDX4 along with other genes; however, no case‑level segregation data or additional familial evidence were provided. A subsequent replication study in an Italian cohort failed to validate the DDX4 association (PMID:23222812), thereby reducing the overall weight of genetic support. These findings suggest that, while there is an initial statistical signal, the genetic evidence alone is insufficient to firmly establish DDX4 as a neuroblastoma susceptibility gene.

Functional studies of DDX4 have primarily focused on its expression and molecular characteristics in non‑tumor contexts. For instance, one study detailed multiple mRNA isoforms in buffalo testis and confirmed high expression levels of the full‑length transcript (PMID:26127001), while another investigation evaluated biophysical properties related to liquid‑liquid phase separation in the protein’s N‑terminal region (PMID:33139563). Despite these detailed functional assessments, no direct mechanistic link with neuroblastoma pathogenesis has been demonstrated. In summary, integration of the current genetic and functional data reveals only limited support for an association between DDX4 and neuroblastoma, with further focused studies needed to clarify its clinical significance. Key take‑home: At present, the association of DDX4 with neuroblastoma remains tentative and should be interpreted with caution in diagnostic and commercial applications.

References

• PLoS Genetics • 2011 • Phenotype restricted genome‑wide association study using a gene‑centric approach identifies three low‑risk neuroblastoma susceptibility Loci. PMID:21436895
• Carcinogenesis • 2013 • Replication of GWAS‑identified neuroblastoma risk loci strengthens the role of BARD1 and affirms the cumulative effect of genetic variations on disease susceptibility. PMID:23222812
• Gene • 2015 • Molecular characterization and expression of buffalo DEAD‑box family VASA gene and mRNA transcript variants isolated from testis tissue. PMID:26127001
• Proceedings of the National Academy of Sciences of the United States of America • 2020 • Comparative roles of charge, Ï, and hydrophobic interactions in sequence‑dependent phase separation of intrinsically disordered proteins. PMID:33139563

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