Growing evidence suggests a major role for Src-homology-2-domain-containing phosphatase 2 (SHP2/PTPN11) in MYCN-driven high-risk neuroblastoma, although biologic confirmation and a plausible mechanism for this contribution are lacking.
Three recurrent genetic aberrations in HRNB (MYCN amplification, TERT re-arrangements, and ATRX mutations) are mutually exclusive and each capable of promoting telomere maintenance mechanisms (i.e., through telomerase or ALT).
Three recurrent genetic aberrations in HRNB (MYCN amplification, TERT re-arrangements, and ATRX mutations) are mutually exclusive and each capable of promoting telomere maintenance mechanisms (i.e., through telomerase or ALT).
A common theme in high-risk neuroblastoma is maintenance of telomeres, one mechanism for which involves alternate lengthening of telomeres (ALT) associated with ATRX gene mutations.
To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed.
To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed.
African genomic ancestry was associated with high-risk neuroblastoma (P = .007) and lower event-free survival (P = .04, hazard ratio = 1.4, 95% confidence interval = 1.05 to 1.80). rs1033069 within SPAG16 (sperm associated antigen 16) was determined to have higher risk allele frequency in the African reference population and statistically significant association with high-risk disease in patients of European and African ancestry (P = 6.42 × 10(-5), false discovery rate < 0.0015) in the overall cohort.
To investigate genetic predispositions for MYCN-amplified neuroblastoma, we performed a meta-analysis of three genome-wide association studies totaling 615 MYCN-amplified high-risk neuroblastoma cases and 1869 MYCN-nonamplified non-high-risk neuroblastoma cases as controls using a fixed-effects model with inverse variance weighting.All statistical tests were two-sided.
Expression analysis revealed that FGFR2 correlates with MYCN amplification and with advanced stage disease, demonstrating the clinical relevance of FGFR2 in NB.
Patients with MYCN(-), high-risk neuroblastoma display a broad, continuous spectrum with regard to response and outcome, whereas MYCN(+) patients either have an excellent response to induction associated with good long-term outcome or develop early progressive disease with a poor outcome.
Here, we report the isolation and propagation of neuroblastoma sphere-forming cells with self-renewal and differentiation potential from tumors of the TH-MYCN mouse, an animal model of high-risk neuroblastoma with MYCN amplification.
Herein, we examined the expression profiles of lncRNAs and protein-coding genes between MYCN amplified and MYCN non-amplified NB from microarray (n = 47) and RNA-seq datasets (n = 493).
Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA's primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma.
The amplification of MYCN correlates with high-risk neuroblastoma and patients with MYCN amplified showed poorer prognosis than those without MYCN amplification.
MYCN amplification is associated with aggressive and advanced stage of high-risk neuroblastoma, which remains difficult to treat and exhibits poor survival under current multimodality treatment.