RNA-Seq Reveals Allele-Specific Expression of Somatic Mutations in Neuroblastoma

Neuroblastoma (NB) is one of the most common solid tumors in children, accounting for approximately 8% of all pediatric malignancies and 15% of childhood cancer deaths. Somatic mutations in several genes such as ALK have been associated with neuroblastoma progression and can facilitate the discovery of novel therapeutic strategies. However, differential expression of mutated and wild-type alleles on the transcriptome level is not well studied. In this study, we analyzed 219 whole-exome sequencing datasets (with somatic mutations detected by MuTect from paired normal and tumor samples) and prioritized mutations in eight candidate genes as potential driver mutations. Meanwhile, we analyzed 127 RNA-seq samples (of which 85 also had DNA-seq data available) for allele-specific expression levels of each mutation. Our integrated analysis of somatic mutations and allele-specific expression levels confirmed the presence of allele-specific expression of somatic mutations in neuroblastoma including MYCN , ALK and PTPN22 . The allele-specific expression of mutations suggests that the same somatic mutation may have different effects on clinical outcomes of tumors. Our study also suggests possible involvement of ZNF44 as a candidate driver gene for neuroblastoma. In summary, this study demonstrates the value of examining allele-specific expression levels of somatic mutations through the analysis of RNA-Seq data to assess the effects of somatic mutations in different patients. Improved understanding of allele-specific expression of somatic mutations can facilitate development of personalized treatment for neuroblastoma in precision medicine.