Transcription instability in high‐risk neuroblastoma is associated with a global perturbation of chromatin domains. Issue 11 (10th October 2017)

• Record Type: Journal Article
• Authors: Zanon, Carlo; Tonini, Gian Paolo
• Is Part Of: Molecular oncology. Volume 11:Issue 11(2017)
• Page Start: 1646
• Page End: 1658
• Publication Date: 2017-10-10
• Subjects: chromatin structural domain -- superenhancer -- transcriptional instability; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12139
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : Chromosome instability has a pivotal role among the hallmarks of cancer, but its transcriptional counterpart is rarely considered a relevant factor in cell destabilization. To examine transcription instability (TIN), we first devised a metric we named TIN index and used it to evaluate TIN on a dataset containing more than 500 neuroblastoma samples. We found that metastatic tumors from high‐risk (HR) patients are characterized by significantly different TIN index values compared to low/intermediate‐risk patients. Our results indicate that the TIN index is a good predictor of neuroblastoma patient's outcome, and a related TIN index gene signature (TIN‐signature) is also able to predict the neuroblastoma patient's outcome with high confidence. Interestingly, we find that TIN‐signature genes have a strong positional association with superenhancers in neuroblastoma tumors. Finally, we show that TIN is linked to chromatin structural domains and interferes with their integrity in HR neuroblastoma patients. This novel approach to gene expression analysis broadens the perspective of genome instability investigations to include functional aspects. Abstract : This study involved the systematic investigation of transcription instability (TIN) as a genome‐wide phenomenon related to cancer. In neuroblastoma, pediatric cancer characterized by a low mutational load, TIN‐related genes has a strong positional association with superenhancers and with chromatin structural domains whose integrity is disrupted in high‐risk compared to low/intermediate‐risk patients.