Translocation (e.g., c-myc in Burkitt's lymphoma), or amplification (e.g., N-myc in neuroblastoma) of myc genes has been causally linked to tumor formation.
Amplification of the MYCN oncogene, a member of the MYC family of transcriptional regulators, is one of the most powerful prognostic markers identified for poor outcome in neuroblastoma, the most common extracranial solid cancer in childhood.
For in vivo validation we selected CSNK1e, a kinase whose expression correlated with MYCN amplification in neuroblastoma (an established MYC-driven cancer).
Our study implicates the role of BORIS/CTCFL in maintenance of stemness and in transition from mesenchymal to epithelial state in MYC amplified neuroblastoma IMR-32 cells.
N-myc is a DNA sequence which shares limited homology to the proto-oncogene c-myc and has been found to be amplified in both primary tissue and cell lines from neuroblastoma, a childhood tumour of neuroectodermal origin.
These data implicate tissue-specific enhancers in defining often highly tumor-specific 'MYC target gene signatures' and identify disruption of the MYCN enhancer regulatory axis as a promising therapeutic strategy in neuroblastoma.
Using neuroblastoma as a tumor model, we established a microRNA (miRNA) signature for activated MYCN/c-MYC signaling in two independent primary neuroblastoma tumor cohorts and provide evidence that c-MYC and MYCN have overlapping functions.
These data suggest that epigenetic and posttranslational inhibition of MYC/MYCN-driven pathways may have significant clinical efficacy against neuroblastoma.
The more complex expression pattern found for the Myc targets in neuroblastomas suggests that genes that were identified originally as targets for c-Myc regulation may be regulated by N-Myc, but other cell specific factors are also needed for transcription of the target genes.
The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential.
Of note, expressions of MCT1 and MCT2 were each significantly elevated in MYCN-amplified neuroblastomas and C-MYC-overexpressing lymphomas than in tumors without MYC overexpression, correlating with poor prognosis and unfavorable patient survival.
MYC and MYCN control the expression of PD-L1 in neuroblastoma cells both <i>in vitro</i> and <i>in vivo</i> Consistently, abundance of PD-L1 transcript correlates with MYC expression in primary neuroblastoma.<b>Conclusions:</b> The combination of PD-L1 and HLA class I represents a novel prognostic biomarker for neuroblastoma.
This hypothesis-driven systems bioinformatics work offered novel insights into the PRC2-mediated tumor cell growth and differentiation in neuroblastoma, which may exert oncogenic effects together with MYC regulation.
To determine whether other modes of myc gene activation underlie progression of some neuroblastomas, 45 were analyzed for amplification of N-myc, c-myc and L-myc and 26 were studied for transcription of these oncogenes.
MYC coordinately regulates polyamine homeostasis as these essential cations support MYC functions, and drugs that antagonize polyamine sufficiency have synthetic-lethal interactions with MYCNeuroblastoma is a lethal tumor in which the MYC homologue MYCN, and ODC1, the rate-limiting enzyme in polyamine synthesis, are frequently deregulated so we tested optimized polyamine depletion regimens for activity against neuroblastoma.
Significant promoter activity in the presence of abundant Myc protein in amplified neuroblastoma lines indicates that autoregulation is disabled in this subset of tumors.
High-risk neuroblastomas (an often lethal embryonal tumor in which MYC activation is paramount) deregulate numerous polyamine enzymes to promote the expansion of intracellular polyamine pools.
Applying this technique, we followed the metaphase location and interphase position of amplified DNA sequences corresponding to the SAMK, MYC, and MYCN genes in four cell lines derived from human tumors: two gastric carcinoma lines (KATO III and SNU-16), a neuroblastoma (NUB-7), and a neuroepithelioma (NUB-20) line.