From fish to FISH: the comparative pathology of neuroblastomas in humans, mice and fish |
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Authors: | Manfred Schwab |
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Institution: | (1) Deutsches Krebsforschungszentrum, Abteilung Zytogenetik-H0400, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany e-mail: m.schwab@dkfz-heidelberg.de Tel.: +49-6221-423220 Fax: +49-6221-423277, DE |
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Abstract: | Neuroblastoma is a malignant cancer of the sympathetic nervous system and is one of the most frequent solid cancers in young
children. Only a few of the many advances in our understanding of basic genetic and cellular mechanisms leading to neuroblastoma
development have translated to clinical practice, and the prognosis for children with neuroblastoma, particularly at advanced
stages, has remained poor. Major directions for neuroblastoma management and control include the application of prognostic
parameters, particularly amplified MYCN, which can be readily visualized by chromosomal fluorescence in situ hybridization (FISH), for individual therapy design,
as well as the initiation of a presymptomatic screening program for early tumor detection to reduce the fraction of advanced-stage
tumors. In addition, new and innovative therapeutic approaches are being sought. The understanding of molecular and cellular
pathways resulting in spontaneous regression in up to 10% of neuroblastoma patients, possibly by apoptosis, could provide
the basis for new biologically based therapeutic interventions. Unlike most other pediatric cancers, neuroblastoma can be
studied in two experimental animal systems. One is the fish system Xiphophorus, where neuroblastomas can be induced in specific strains by exposure to mutagens/carcinogens; the second is mice that carry
MYCN as a transgene. These animal systems demonstrate that neuroblastomas are evolutionarily conserved tumors. Their study could
well result in a better understanding of neuroblastoma development. At the same time they represent systems in which experimental
therapies can be preclinically tested.
Received: 31 October 1998 / Accepted: 12 November 1998 |
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Keywords: | Cancer in fish Melanoma Experimental model Chromosomes Susceptibility Transgenic mice MYCN Oncogenes Amplification Translocation Carcinogenesis Pediatric cancer FISH |
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