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.
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 8-10 000 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 2 kb 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.
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York, USA.
Khalid
K
Sossey-Alaoui
Guanfang
G
Su
Eda
E
Malaj
Bruce
B
Roe
John K
JK
Cowell
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002882:Chromosomes, Human, Pair 13; D003001:Cloning, Molecular; D018305:Ganglioneuroblastoma / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D051300:Wiskott-Aldrich Syndrome Protein Family
D000199:Actins; D008840:Microfilament Proteins; C120153:WASF3 protein, human; C485623:Wasf3 protein, mouse; D051300:Wiskott-Aldrich Syndrome Protein Family