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      Neuroblastoma, a Paradigm for Big Data Science in Pediatric Oncology

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          Abstract

          Pediatric cancers rarely exhibit recurrent mutational events when compared to most adult cancers. This poses a challenge in understanding how cancers initiate, progress, and metastasize in early childhood. Also, due to limited detected driver mutations, it is difficult to benchmark key genes for drug development. In this review, we use neuroblastoma, a pediatric solid tumor of neural crest origin, as a paradigm for exploring “big data” applications in pediatric oncology. Computational strategies derived from big data science–network- and machine learning-based modeling and drug repositioning—hold the promise of shedding new light on the molecular mechanisms driving neuroblastoma pathogenesis and identifying potential therapeutics to combat this devastating disease. These strategies integrate robust data input, from genomic and transcriptomic studies, clinical data, and in vivo and in vitro experimental models specific to neuroblastoma and other types of cancers that closely mimic its biological characteristics. We discuss contexts in which “big data” and computational approaches, especially network-based modeling, may advance neuroblastoma research, describe currently available data and resources, and propose future models of strategic data collection and analyses for neuroblastoma and other related diseases.

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          Most cited references145

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          Network analysis in the social sciences.

          Over the past decade, there has been an explosion of interest in network research across the physical and social sciences. For social scientists, the theory of networks has been a gold mine, yielding explanations for social phenomena in a wide variety of disciplines from psychology to economics. Here, we review the kinds of things that social scientists have tried to explain using social network analysis and provide a nutshell description of the basic assumptions, goals, and explanatory mechanisms prevalent in the field. We hope to contribute to a dialogue among researchers from across the physical and social sciences who share a common interest in understanding the antecedents and consequences of network phenomena.
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            Metastasis: a question of life or death.

            The metastatic process is highly inefficient--very few of the many cells that migrate from the primary tumour successfully colonize distant sites. One proposed mechanism to explain this inefficiency is provided by the cancer stem cell model, which hypothesizes that micrometastases can only be established by tumour stem cells, which are few in number. However, recent in vitro and in vivo observations indicate that apoptosis is an important process regulating metastasis. Here we stress that the inhibition of cell death, apart from its extensively described function in primary tumour development, is a crucial characteristic of metastatic cancer cells.
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              The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report.

              Because current approaches to risk classification and treatment stratification for children with neuroblastoma (NB) vary greatly throughout the world, it is difficult to directly compare risk-based clinical trials. The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. The statistical and clinical significance of 13 potential prognostic factors were analyzed in a cohort of 8,800 children diagnosed with NB between 1990 and 2002 from North America and Australia (Children's Oncology Group), Europe (International Society of Pediatric Oncology Europe Neuroblastoma Group and German Pediatric Oncology and Hematology Group), and Japan. Survival tree regression analyses using event-free survival (EFS) as the primary end point were performed to test the prognostic significance of the 13 factors. Stage, age, histologic category, grade of tumor differentiation, the status of the MYCN oncogene, chromosome 11q status, and DNA ploidy were the most highly statistically significant and clinically relevant factors. A new staging system (INRG Staging System) based on clinical criteria and tumor imaging was developed for the INRG Classification System. The optimal age cutoff was determined to be between 15 and 19 months, and 18 months was selected for the classification system. Sixteen pretreatment groups were defined on the basis of clinical criteria and statistically significantly different EFS of the cohort stratified by the INRG criteria. Patients with 5-year EFS more than 85%, more than 75% to or = 50% to < or = 75%, or less than 50% were classified as very low risk, low risk, intermediate risk, or high risk, respectively. By defining homogenous pretreatment patient cohorts, the INRG classification system will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world and the development of international collaborative studies.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                27 December 2016
                January 2017
                : 18
                : 1
                : 37
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55902, USA; Salazar.Brittany@ 123456mayo.edu
                [2 ]Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Balczewski.Emily@ 123456mayo.edu (E.A.B.); Ung.ChoongYong@ 123456mayo.edu (C.Y.U.)
                Author notes
                [* ]Correspondence: Zhu.Shizhen@ 123456mayo.edu ; Tel.: +1-507-293-2558; Fax: +1-507-293-1058
                [†]

                These authors contributed equally to this work.

                Article
                ijms-18-00037
                10.3390/ijms18010037
                5297672
                28035989
                20726fc1-2da4-4e8c-8e20-b26b742e1626
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 October 2016
                : 17 December 2016
                Categories
                Review

                Molecular biology
                neuroblastoma,big data,computational modeling,drug repositioning,networks,spontaneous regression,metastasis

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