This study demonstrates that targeted expression of the MYCN proto-oncogene in transgenic mice leads to the development of neuroblastoma. The researchers created transgenic mice that overexpress MYCN in neuroectodermal cells and observed the development of neuroblastoma several months after birth. Analysis of the tumors using comparative genomic hybridization (CGH) revealed gains and losses of chromosomal regions that are syntenic with those observed in human neuroblastomas. These findings suggest that MYCN can contribute to the genesis of neuroblastoma and that genetic events involved in neuroblastoma can occur in multiple chronological sequences. The study also shows that increases in MYCN dosage or deficiencies in tumor suppressor genes such as NF1 or RBI can enhance tumorigenesis. The results provide direct evidence that MYCN contributes to neuroblastoma and offer a model for further study of neuroblastoma pathogenesis and therapy. The transgenic mice developed neuroblastomas with histological features similar to those in human neuroblastomas, including neuronal differentiation, ganglionic elements, and synaptophysin and neuron-specific enolase positivity. The tumors also showed synapse formation and neurosecretory granules, and exhibited chromosomal gains and losses in regions syntenic with those in human neuroblastomas. The study further shows that the expression of MYCN in the neuroectoderm predisposes mice to neuroblastoma, and that the genetic lesions involved in neuroblastoma development are similar in mice and humans. The findings suggest that MYCN amplification may occur early in a subset of neuroblastomas, leading to more aggressive tumors. However, it is unlikely that MYCN amplification is the initial event in tumorigenesis, as it does not occur in normal mammalian cells. Instead, early genetic events may promote genomic instability, allowing cells to tolerate such instability and be transformed by lesions such as MYCN amplification. The study also shows that additional genetic lesions, such as loss of NF1 or RBI, can contribute to tumorigenesis in mice overexpressing MYCN. The results suggest that the genetic pathways contributing to mouse neuroblastoma are similar to those observed in human tumors. The findings highlight the importance of studying the genetic events involved in neuroblastoma and provide a valuable model for further research into the pathogenesis and therapy of this disease.This study demonstrates that targeted expression of the MYCN proto-oncogene in transgenic mice leads to the development of neuroblastoma. The researchers created transgenic mice that overexpress MYCN in neuroectodermal cells and observed the development of neuroblastoma several months after birth. Analysis of the tumors using comparative genomic hybridization (CGH) revealed gains and losses of chromosomal regions that are syntenic with those observed in human neuroblastomas. These findings suggest that MYCN can contribute to the genesis of neuroblastoma and that genetic events involved in neuroblastoma can occur in multiple chronological sequences. The study also shows that increases in MYCN dosage or deficiencies in tumor suppressor genes such as NF1 or RBI can enhance tumorigenesis. The results provide direct evidence that MYCN contributes to neuroblastoma and offer a model for further study of neuroblastoma pathogenesis and therapy. The transgenic mice developed neuroblastomas with histological features similar to those in human neuroblastomas, including neuronal differentiation, ganglionic elements, and synaptophysin and neuron-specific enolase positivity. The tumors also showed synapse formation and neurosecretory granules, and exhibited chromosomal gains and losses in regions syntenic with those in human neuroblastomas. The study further shows that the expression of MYCN in the neuroectoderm predisposes mice to neuroblastoma, and that the genetic lesions involved in neuroblastoma development are similar in mice and humans. The findings suggest that MYCN amplification may occur early in a subset of neuroblastomas, leading to more aggressive tumors. However, it is unlikely that MYCN amplification is the initial event in tumorigenesis, as it does not occur in normal mammalian cells. Instead, early genetic events may promote genomic instability, allowing cells to tolerate such instability and be transformed by lesions such as MYCN amplification. The study also shows that additional genetic lesions, such as loss of NF1 or RBI, can contribute to tumorigenesis in mice overexpressing MYCN. The results suggest that the genetic pathways contributing to mouse neuroblastoma are similar to those observed in human tumors. The findings highlight the importance of studying the genetic events involved in neuroblastoma and provide a valuable model for further research into the pathogenesis and therapy of this disease.