RNA-Sequencing Combined With Genome-Wide Allele-Specific Expression Patterning Identifies ZNF44 Variants as a Potential New Driver Gene for Pediatric Neuroblastoma.

INTRODUCTION

Neuroblastoma (NB) is one of the children's most common solid tumors, accounting for approximately 8% of pediatric malignancies and 15% of childhood cancer deaths. Somatic mutations in several genes, such as , have been associated with NB progression and can facilitate the discovery of novel therapeutic strategies. However, the differential expression of mutated and wild-type alleles on the transcriptome level is poorly studied.

METHODS

This study analyzed 219 whole-exome sequencing datasets with somatic mutations detected by MuTect from paired normal and tumor samples.

RESULTS

We prioritized mutations in 8 candidate genes (, , , , , , , and ) as potential driver mutations. We further confirmed the presence of allele-specific expression of the somatic mutations in NB with integrated analysis of 127 RNA-seq samples (of which 85 also had DNA-seq data available), including , , and . The allele-specific expression of mutations suggests that the same somatic mutation may have different effects on the clinical outcomes of tumors.

CONCLUSION

Our study suggests 2 novel variants of as a novel candidate driver gene for NB.