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(American Journal of Pathology. 2001;158:663-672.)
© 2001 American Society for Investigative Pathology

Regular Article

Expression of SMARCF1, a Truncated Form of SWI1, in Neuroblastoma

Tamotsu Takeuchi^*, Sophie Nicole, Akiko Misaki^*, Mutsuo Furihata^*, Jun Iwata, Hiroshi Sonobe^* and Yuji Ohtsuki^*

From the Department of Pathology,^*
Kochi Medical School, Kochi, Japan; the Department of Laboratory Investigation,
Kochi Municipal Central Hospital, Kochi, Japan; and the Laboratoire des Pathologies de la Myéline,
INSERM CJF9711, Faculté de Médecine de la Pitiê-Salpêtrière 105, Paris, France

Previously we cloned and mapped a B120 gene to human chromosome 1p35-36.1 where possible suppressor genes for various neuroendocrine tumors including neuroblastoma have been mapped. Very recently, B120 was identified as a truncated form of p270, a putative human counterpart of SWI1. In the present study, expression of the B120 gene product was immunohistochemically investigated in 23 neuroblastomas. We also examined B120 expression in neural stem cells in developing brain and intact adrenal medulla. Four of 23 neuroblastomas strongly expressed B120 gene product in both cytoplasm and nucleus. The other neuroblastomas expressed B120 gene product in the nucleus; however, the intensity of staining was much weaker and equivalent to that in developing human brain stem cells in the subventricular region. B120 gene product was less strongly expressed in intact adrenal medulla. Subsequently, we performed loss of heterozygosity studies on 19 neuroblastomas using the polymorphic markers D1S195 and D1S511 located near the B120 gene. Loss of heterozygosity was observed in three of 19 tumors that abundantly expressed B120 protein. Furthermore, neuroblastoma cells were transfected with B120 expression vector. These transfected neuroblastoma cells adhered to each other and aggregated. Differential display experiments followed by reverse transcriptase-polymerase chain reaction and Northern blot analysis were performed and three molecules with altered expression in B120-transfected neuroblastoma cells were identified. One of three genes seemed to be a proliferation-related and cell cycle-related nucleolar protein, p120, encoding gene. We further characterized the genomic structure of B120. B120 appeared to be encoded by 17 exons in more than 20-kbp genomic DNA. The present findings contribute to understanding of the B120 gene, a truncated form of human SWII1, an approved term for which is SMARCF1, in normal cells and neuroblastomas.

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