Abstract
Next-generation sequencing (NGS) technologies have revolutionized cancer genomics due to their high throughput sequencing capacity. Reports of the gene mutation profiles of various cancers by many researchers, including international cancer genome research consortia, have increased over recent years. In addition to detecting somatic mutations in tumor cells, NGS technologies enable us to approach the subject of carcinogenic mechanisms from new perspectives. Deep sequencing, a method of optimizing the high throughput capacity of NGS technologies, allows for the detection of genetic aberrations in small subsets of premalignant and/or tumor cells in noncancerous chronically inflamed tissues. Genome-wide NGS data also make it possible to clarify the mutational signatures of each cancer tissue by identifying the precise pattern of nucleotide alterations in the cancer genome, providing new information regarding the mechanisms of tumorigenesis. In this review, we highlight these new methods taking advantage of NGS technologies, and discuss our current understanding of carcinogenic mechanisms elucidated from such approaches.
Highlights
Paediatric cancers—like neuroblastoma—transpire during the neonatal epoch of an infant [1].Neuroblastoma are solid malignant tumours which are widely diagnosed during infancy [2,3,4] and are the second most common paediatric tumours representing about 10% of all paediatric cancers [5]
Cancers 2015, 7 to the childhood and adolescent cancer statistics published by the American Cancer Society (2014), neuroblastoma (7%) is the third most frequent cancer in childhood only preceded by acute lymphocytic leukaemia (26%) and cancers of the brain and CNS (21%) [6]
Cisplatin induced increase in [Ca2+ ]i is allied with a cellular apoptosis with the activation of calpain and not caspase-8, confirming that cisplatin induced calcium influx via the IP3 receptors lead to cellular apoptosis with the activation of calpain [22]
Summary
Paediatric cancers—like neuroblastoma—transpire during the neonatal epoch of an infant [1]. Increase of [Ca2+ ]i either from the extracellular space or from the internal stores upon treatment of neuroblastoma cell lines with several GPCR ligands like retinoic acid as in current neuroblastoma treatment, Sigma 2 ligands and other compounds like cisplatin, arsenic trioxide or tri-methyl-tin chloride (TMT) results either in differentiation or induction of apoptosis (Figure 2) This confers the role of [Ca2+ ]i in inducing these pathways in the neuroblastoma cells and an insight into the possible role of [Ca2+ ]i in the development and an efficient mechanism of action for the treatment of neuroblastoma. Studies have confirmed the role of [Ca2+ ]i in inducing necroptosis in human neuroblastoma cells (Figure 3) via the activation of receptor interacting protein kinase 1 (RIP1) by the CAMKK [125]. Cisplatin induced increase in [Ca2+ ]i is allied with a cellular apoptosis with the activation of calpain and not caspase-8, confirming that cisplatin induced calcium influx via the IP3 receptors lead to cellular apoptosis with the activation of calpain [22]
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