Abstract
Neuroblastoma (Nb) is a malignancy of the sympathetic nervous system which affects children in their first decade. It is the most common extra-cranial solid tumor in children with an incidence of approximately 1 in 8â10â000 live births annually and accounts for approximately 10% of all children's cancers. Ganglioneuroblastoma is a relatively benign form of Nb and consists of a mixture of fibrils, mature and maturing ganglion cells, as well as undifferentiated neuroblasts. During routine cytogenetic analysis of patients with different manifestations of neuroblastoma we have identified one patient with ganglioneuroblastoma that carries an apparently balanced t(1:13)(q21:q12) reciprocal translocation. Positional cloning of the translocation breakpoint on chromosome 13 resulted in the mapping of the breakpoint between coding exon 2 and exon 3 of WAVE3, a member of WASP gene family. Although the breakpoint region on chromosome 1 was localized to within 2âkb of genomic sequence, no gene was found to be interrupted on this chromosome. The WAVE3 transcript is mainly expressed in the nervous system and, like all the members of the WASP gene family, WAVE3 is a key element in actin polymerization and cytoskeleton organization. WAVE3, therefore, is important for cell differentiation and motility and its expression is lost in a number of low grade and stage 4S tumors. From analysis of its expression pattern and function, WAVE3 is a candidate tumor suppressor gene, at least in some forms of neuroblastoma.
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Acknowledgements
The authors wish to acknowledge NIH grant NS35791 which supported this work as well as the Roswell Park Cancer Center Support Grant (P30 CA 16056â26). We are grateful to the Children's Oncology Group for providing tumor samples for this study. We would also like to thank Eiko Kitamura, Ph.D. and Karen Head, MS and Lisa Wylie for their technical assistance.
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Sossey-Alaoui, K., Su, G., Malaj, E. et al. WAVE3, an actin-polymerization gene, is truncated and inactivated as a result of a constitutional t(1;13)(q21;q12) chromosome translocation in a patient with ganglioneuroblastoma. Oncogene 21, 5967â5974 (2002). https://doi.org/10.1038/sj.onc.1205734
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DOI: https://doi.org/10.1038/sj.onc.1205734
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