title: Neuroblastoma models for insights into tumorigenesis and new therapies.
abstract: BACKGROUND
  Neuroblastoma is the most common extracranial solid tumor in children. It occurs in the adrenosympathetic lineage, which is derived from the neural crest. MYCN amplification is found in about 20% of cases and is the most powerful prognostic factor. Anaplastic lymphoma kinase (ALK) mutation is also found in 7% of sporadic neuroblastomas and 50% of familial neuroblastomas. Although several mutations other than ALK are also found, about 70% of neuroblastomas show no mutations. Another important feature of neuroblastoma is that it sometimes spontaneously regresses. These features collectively suggest that neuroblastoma is caused by aberrations in the normal development processes of the neural crest.
  
  
  METHODS
  This review highlights a number of models of neuroblastoma including genetically engineered mouse models (GEMMs). The main GEMMs described here are: tyrosine hydroxylase (TH)-MYCN, TH-MYCN/Trp53(+/-), TH-MYCN/TH-Cre/Casp8(flox/flox), TH-MYCN/TH-ALK(F1174L) and DBH-iCre/CAG-LSL-Lin28b.
  
  
  CONCLUSIONS
  The current mouse models available are very useful for investigating the mechanisms of tumorigenesis and for developing therapeutics. However, many aspects have not yet been addressed. These include immediate early events after tumor initiation, epigenetic changes, spontaneous regression and metastasis. On the other hand, the current models do not perfectly recapitulate features of human neuroblastoma. Therefore, humanized mice and new GEMMs should be also considered for future research.
authors.affiliation: Nagoya University Graduate School of Medicine, Department of Biochemistry , Nagoya , Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kiyonari
authors.forename: Kenji
authors.initials: K
authors.lastname: Kadomatsu
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003131:Combined Modality Therapy; D008822:Mice, Transgenic; D009154:Mutation; D000071447:N-Myc Proto-Oncogene Protein; D009374:Neoplasms, Experimental; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C571825:MYCN protein, mouse; D000071447:N-Myc Proto-Oncogene Protein; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: MYCN; anaplastic lymphoma kinase; genetically engineered mouse; neural crest; neuroblastoma