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. 2017 Jan 5;17(1):20.
doi: 10.1186/s12885-016-2986-6.

Growth, progression and chromosome instability of Neuroblastoma: a new scenario of tumorigenesis?

Gian Paolo Tonini  1
Affiliations

Growth, progression and chromosome instability of Neuroblastoma: a new scenario of tumorigenesis?

Gian Paolo Tonini. BMC Cancer. .

Abstract

Background: Neuroblastoma 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.

Conclusions: In 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.

Keywords: Aneuploidy; Chromosome instability; Embryo; Genome; Neural crest cells; Neuroblastoma.

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Figures

Fig. 1
Fig. 1
Distribution of the DNA index value of 2994 neuroblastoma tumors belonging to Italian Neuroblastoma Register [2]. The DNA index percentage value for each clinical stage is reported in the upper panel (red color). On the left, green value are referred to the 1.0 for diploid cells, 1.5 and 2.00 for hyperdiploid cells. A DNA index of 1.50 is more frequent in tumors of patients who are younger than 18 months for all stages but not for stage 4 patients who have a peak of 43% DNA of diploid cells. Tumors of patients over 18 months of age primarily show a DNA diploid tumor cells with a peak (62%) of tumor cells in stage 4. Stage 4S is not represented because occurs in patients under 12 months of age, by definition
Fig. 2
Fig. 2
Distribution of stage 4 and stage 4S Italian patients from the National Neuroblastoma Register according to the age of the patients at diagnosis. Most of the stage 4S cases are observed between 0 and 6 months. On the contrary, the frequency of stage 4 cases increases after 6 months of observation
See this image and copyright information in PMC

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