![]() ![]() This model delivered many valuable insights into neuroblastomagenesis. TH- MYCN mice express the human MYCN gene under the control of the rat tyrosine hydroxylase (Th) promotor, which results in neuroblastic tumors in about 50% of transgenic animals. Relevant features to study are tumor localization, histology, metastatic pattern as well as genomic features such as RNA expression, DNA copy number alterations and mutation profiles.įor almost two decades, only one transgenic mouse model for neuroblastoma was available (TH- MYCN). One of the important issues is to determine to what extent the mouse model faithfully recapitulates the human disease and therefore how well it may serve as a preclinical model. Furthermore, facing the emerging challenges of combination treatments of novel drugs, these models now facilitate close alignment of in vivo preclinical and early clinical studies. They enable, amongst others, the analysis of cooperative genetic events, dynamic regulation of perturbed gene expression during tumor formation and the study of tumor clonality and heterogeneity. Mouse models are essential tools in the study of the molecular pathogenesis of cancer. Taken together, our study further supports the validity of the tested mouse models for mechanistic and preclinical studies of human neuroblastoma. Despite low mutational load, the genes mutated in murine disease were found to be enriched for genes mutated in human disease. Gene copy number alterations are the hallmark of both murine and human disease and frequently affect syntenic genomic regions. The murine tumors revealed a low number of genomic alterations – in keeping with human neuroblastoma - and a positive correlation of the number of genetic lesions with the time to onset of tumor formation was observed. Here, we report on the further genomic characterization through exome sequencing and DNA copy number analysis of four of the currently available murine neuroblastoma model systems ( ALK, Th- MYCN, Dbh- MYCN and Lin28b). Recently, novel mouse models for neuroblastoma have been developed. To optimally serve these goals, it is essential that the mouse model faithfully recapitulates the human disease. ![]() Genetically engineered mouse models have proven to be essential tools for unraveling fundamental aspects of cancer biology and for testing novel therapeutic strategies. Received: MaAccepted: OctoPublished: December 22, 2017 Bram De Wilde 1, 2, Anneleen Beckers 1, Sven Lindner 3, Althoff Kristina 3, Katleen De Preter 1, 2, Pauline Depuydt 1, 2, Pieter Mestdagh 1, 2, Tom Sante 1, Steve Lefever 1, 2, Falk Hertwig 4, 5, Zhiyu Peng 6, Le-Ming Shi 7, Sangkyun Lee 8, Elien Vandermarliere 9, 10, Lennart Martens 9, 10, Björn Menten 1, Alexander Schramm 3, Matthias Fischer 4, 5, Johannes Schulte 11, Jo Vandesompele 1, 2 and Frank Speleman 1, 2ġCenter for Medical Genetics, Ghent University, Ghent, BelgiumĢCancer Research Institute Ghent, Ghent University, Ghent, BelgiumģDepartment of Pediatric Oncology and Hematology, University Children’s Hospital, Essen, GermanyĤDepartment of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Cologne, GermanyĥCenter for Molecular Medicine Cologne, University of Cologne, Cologne, GermanyĦBGI-Shenzhen, Bei Shan Industrial Zone, Yantian District, Shenzhen, Guangdong, ChinaħCenter for Pharmacogenomics and Fudan-Zhangjiang Center for Clinical Genomics, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, ChinaĨDepartment of Computer Science, Artificial Intelligence Group, TU Dortmund, Dortmund, GermanyĩMedical Biotechnology Center, VIB, Ghent, Belgiumġ0Department of Biochemistry, Ghent University, Ghent, Belgiumġ1Pediatric Oncology and Hematology, Charité University Medicine, Berlin, Germanyįrank Speleman, email: neuroblastoma mouse model exome sequencing array CGH
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