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LATEST UPDATES » Vol 24, No. 10, October 2020 – Artificial Intelligence Technologies — Helping the Fight Against COVID-19s       » Improving Sensitivity of Optical Receivers for Space Communication       » Genetic Variants Identified for the Susceptibility to Neuroblastoma       » Novo Nordisk Launches New Treatment for Diabetes in Singapore       » SMART Researchers Find New Way to Make Bacteria More Sensitive to Antibiotics       » Study Finds Liver Injury to be Common Among COVID-19 Patients      
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EYE ON CHINA
Genetic Variants Identified for the Susceptibility to Neuroblastoma
Study reveals new relationship between genetic variant in an RNA helicase that could explain the predisposition to sporadic neuroblastoma within the Chinese population.

Neuroblastoma is the most common solid extra-cranial tumour diagnosed during childhood. It is responsible for 15 percent of all childhood malignancy-related deaths. Despite the presence of multiple cytotoxic therapies and advanced immunotherapies that can be applied, survival rate of neuroblastoma patients is below 50 percent.

The genetic explanations behind the occurrence of sporadic neuroblastoma still remains largely unclear. There however have been discoveries made in identifying genetic variants which correspond to increased risk of neuroblastoma. Presently known genetic variants only account for a small proportion of neuroblastoma cases. Certain functional polymorphisms are still overlooked by DNA chip-based GWAS (Genome-Wide Association Studies). Much research is required to identify genetic variants that result in predisposition to neuroblastoma, particularly those for specific populations.

In a study by researchers from multiple research institutes, found through a screening strategy of functional gene polymorphism to discover a genetic variant associated with neuroblastoma susceptibility.

"According to the screening strategy of functional gene polymorphism, we have achieved some results. For example, screening strategy designed for polymorphism targeted by MYCN and important functional gene polymorphism sites missed by GWAS chip ". Said Professor Guo, corresponding author of this article.

The MYCN gene is an oncogene which is part of the Myc family of oncogenes. It is known to play key roles in regulating cell proliferation and apoptosis. MYCN is also found to be amplified in aggressive forms of neuroblastoma and is associated with undifferentiated phenotype and poor prognosis.

In this study, the team focused on an RNA helicase known as the DEAD box 1 (DDX1) which is known to be involved in neuroblastoma progression. Its polymorphisms and association with neuroblastoma still remain unclear.

“DDX1 loci is located very close to the MYCN gene, it was predicted that it may be cis-regulated by MYCN. We also found that highly expressed DDX1 is closely associated to poor survival of neuroblastoma." Shared Professor Guo.

The team uncovered that a specific genetic variation resulting in increased DDX1 expression is associated with susceptibility to neuroblastoma. MYC-associated protein X (MAX) a transcription factor displayed strong affinity to the C allele at polymorphism on the DDX1 promoter compared to the T allele.

“Interestingly, MYCN gene can activate the reporter activity of DDX1 promoter, but cannot bind to the promoter alone. This result is consistent with its way of working, like all members of the MYC family, requiring interaction with members of the MAX family to form a functional transcription factor." Said Dr Jin, first author of this work.

The research systematically revealed the relationship between MYCN-related variants and neuroblastoma susceptibility in the Chinese population, and provided mechanisms for this genetic variant.

This work was supported by grants from the National Natural Science Foundation of China, Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education, Clinical Application Research Funds of Capital Beijing, Beihang University & Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan, The Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority.

 

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