Abstract
BackgroundNeuroblastoma is a pediatric cancer with a low survival rate of patients with metastatic stage 4 disease. Tumor aggressiveness and progression have been associated with structural copy number variations (CNVs) that are observed in malignant cells. In contrast, localized Neuroblastomas, which are associated with a low number of structural CNVs but frequent numerical CNVs, are less aggressive, and patients have good outcomes. Finally, whole-genome and whole-exome sequencing of Neuroblastoma tissues have shown few damaging mutations in these tumors.ConclusionsIn the present report it is proposed that chromosome instability (CIN) plays a major role in Neuroblastoma tumorigenesis and that CIN is already present in the early phases of tumor development. High CIN can promote several types of chromosomal damage including chromothripsis, gene deletion, amplification and rearrangements, which deregulate gene expression. Indeed, gene rearrangements have been reported as a new scenario in the development of Neuroblastoma, which supports the hypothesis that CIN is an early step preliminary to the late catastrophic events leading to tumor development.
Highlights
A high number of both numerical and structural copy number variations (CNVs) indicates chromosome instability (CIN) in Neuroblastoma Clinical observations strongly support the notion that the course of stage 4S Neuroblastoma is initiated with non-aggressive behavior during embryonic life and that this tumor continues to develop during infancy [14] (see : The European study, LINES 2009 (Low and Intermediate Risk Neuroblastoma European Study), ClinicalTrials.gov Identifier: NCT01728155)
This is supported by the fact that tumors of stage 4S patients have several numerical CNVs, whereas stage 4 tumors are characterized by a high number of structural CNVs [10]
Neuroblastoma: a CIN disease In conclusion, currently, sufficient biological, molecular and clinical observations have been made, which allowed us to hypothesize that the embryonic development of Neuroblastoma is a consequence of high chromosome instability of neural crest cells
Summary
Neuroblastoma: a CIN disease In conclusion, currently, sufficient biological, molecular and clinical observations have been made, which allowed us to hypothesize that the embryonic development of Neuroblastoma is a consequence of high chromosome instability of neural crest cells. Peifer and colleagues conclude that genome remodeling is the cause of telomerase gene activation. This finding supports the hypothesis that genome instability is an early event in Neuroblastoma tumorigenesis. The large amount of genomic data on Neuroblastoma and several clinical observations in regards to the natural history of the disease allow us to propose that Neuroblastoma arises due to the chromosome instability present in neural crest cells.
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