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Semin Cancer Biol. 2011 Oct;21(4):276-82. doi: 10.1016/j.semcancer.2011.09.002. Epub 2011 Sep 16.

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage.

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Center for Molecular Pathology, Department of Laboratory Medicine, CREATE Health, Lund University, Skåne University Hospital, Malmö, Sweden.


Neuroblastoma is a childhood malignancy of the sympathetic neuronal lineage. It is a rare disease, but since it is frequently diagnosed during infancy, neuroblastoma causes life-long medical follow up of those children that survive the disease. It was early recognized that a high tumor cell differentiation stage correlates to favorable clinical stage and positive clinical outcome. Today, highly differentiated tumors are surgically removed and not further treated. Cells of many established human neuroblastoma cell lines have the capacity to differentiate when stimulated properly, and these cell lines have been used as models for studying and understanding central concepts of tumor cell differentiation. One recent aspect of this issue is the observation that tumor cells can dedifferentiate and gain a stem cell-like phenotype during hypoxic conditions, which was first shown in neuroblastoma. Aberrant or blocked differentiation is a central aspect of neuroblastoma genesis. In this review we summarize known genetic and non-genetic events in neuroblastoma that might be coupled to an aberrant sympathetic neuronal differentiation and thereby indirectly influencing tumorigenesis and/or aggressive neuroblastoma behavior.

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