Whole exome sequencing of high-risk neuroblastoma identifies novel non-synonymous variants

Abstract

Neuroblastoma (NBL), one of the main death-causing cancers in children, is known for its remarkable genetic heterogeneity and varied patient outcome spanning from spontaneous regression to widespread disease. Specific copy number variations and single gene rearrangements have been proven to be associated with biological behavior and prognosis; however, there is still an unmet need to enlarge the existing armamentarium of prognostic and therapeutic targets. We performed whole exome sequencing (WES) of samples from 18 primary tumors and six relapse samples originating from 18 NBL patients. Our cohort consists of 16 high-risk, one intermediate, and one very low risk patient. The obtained results confirmed known mutational hotspots in ALK and revealed other non-synonymous variants of NBL-related genes (TP53, DMD, ROS, LMO3, PRUNE2, ERBB3, and PHOX2B) and of genes cardinal for other cancers (KRAS, PIK3CA, and FLT3). Beyond, GOSeq analysis determined genes involved in biological adhesion, neurological cell-cell adhesion, JNK cascade, and immune response of cell surface signaling pathways. We were able to identify novel coding variants present in more than one patient in nine biologically relevant genes for NBL, including TMEM14B, TTN, FLG, RHBG, SHROOM3, UTRN, HLA-DRB1, OR6C68, and XIRP2. Our results may provide novel information about genes and signaling pathways relevant for the pathogenesis and clinical course in high-risk NBL.

Exploration of Potential Target Genes of miR-24-3p in Chicken Myoblasts by Transcriptome Sequencing Analysis

“…Among all the genes tested in this study, those whose expression level showed p -adjust ≤ 0.05 were assigned as differentially expressed genes (DEGs). Moreover, the gene ontology (GO) enrichment and KEGG pathway analysis of the DEGs were implemented with GO-seq (R-3.3.2) and KOBAS (v2.0) [ 19 , 20 ], respectively. We determined the significant degree of GO enrichment and KEGG pathways by the standard of p -value ≤ 0.05 in the comparison group mimic vs. NC.…”

Exploring the role of HLA variants in neuroblastoma susceptibility through whole exome sequencing

“…7 Furthermore, primary tumours have been found to harbour somatic coding mutations in the ALK and ATRX genes, as well as non-coding mutations within regulatory regions. [8][9][10][11] These mutations are recognised as oncogenic drivers and have potential prognostic value. Additionally, gene expression profiles have demonstrated predictive power regarding clinical outcomes, particularly in high-risk NB patients.…”

“…For children over 6 years of age, structural variations are distinct, with loss of 19p and gain of 1q being the most prevalent 7 . Furthermore, primary tumours have been found to harbour somatic coding mutations in the ALK and ATRX genes, as well as non‐coding mutations within regulatory regions 8–11 . These mutations are recognised as oncogenic drivers and have potential prognostic value.…”