J. Takita and M. Ishii contributed equally to this article.
Gene expression profiling and identification of novel prognostic marker genes in neuroblastoma
Version of Record online: 26 MAR 2004
Copyright © 2004 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 40, Issue 2, pages 120–132, June 2004
How to Cite
Takita, J., Ishii, M., Tsutsumi, S., Tanaka, Y., Kato, K., Toyoda, Y., Hanada, R., Yamamoto, K., Hayashi, Y. and Aburatani, H. (2004), Gene expression profiling and identification of novel prognostic marker genes in neuroblastoma. Genes Chromosom. Cancer, 40: 120–132. doi: 10.1002/gcc.20021
- Issue online: 14 APR 2004
- Version of Record online: 26 MAR 2004
- Manuscript Accepted: 28 JAN 2004
- Manuscript Received: 29 JUL 2003
- Ministry of Health and Welfare of Japan
- Ministry of Education, Culture, Sports, Science and Technology, Japan
To investigate the various genetic characteristics of and differences between early- and advanced-stage neuroblastoma (NB) and to identify candidate genes involved in NB progression, we performed DNA microarray analysis on 20 primary tumors. Two-way clustering analysis based on the expression pattern of approximately 500 of 1,700 genes revealed genetic subgroups in these NB tumors. Although 9 of the 13 early-stage tumors (69%) and 4 of the 6 advanced-stage tumors (67%) were classified as being in the same cluster, the remaining tumors showed different expression profiles. This indicates that both the early- and advanced-stage tumors were heterogeneous. Based on the microarray data, we identified the BIRC, CDKN2D, and SMARCD3 genes as those that are predominantly expressed in either the early or the advanced stage of NB. These genes have been reported to be associated with apoptosis, cell cycles, and the transcriptional activator, respectively. To better assess the prognostic value of the expression of these genes in NB, real-time polymerase chain reaction was carried out on 50 primary tumors. The expression of both the BIRC3 and CDKN2D genes was significantly higher in the early-stage group than in the advanced-stage group (P = 0.002 and 0.003, respectively), whereas the expression of the SMARCD3 gene was significantly reduced in the early-stage group (P = 0.02). Therefore, the BIRC, CDKN2D, and SMARCD3 genes are possible candidates for being novel prognostic markers for NB. © 2004 Wiley-Liss, Inc.