| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
In spite of recent progress in cancer therapy, the overall survival rate of the patients with neuroblastoma in advanced stages is still quite low. Furthermore, prognostic markers currently used are sometimes not enough to predict prognosis of the patients with intermediate risk type of tumors. The main purpose of this study is to construct a system for early classification of such tumors and to help choose appropriate therapeutic strategy, through the analyses of genomic aberrations and expression profiling of neuroblastoma samples. In this study, following results were obtained :
1) Expression profiling of neuroblastoma
We previously made an in-house, tumor-proper cDNA chip harboring the 11,000 genes collected from primary neuroblastomas. The chip was applied to the expression profiling of neuroblastomas with various prognoses. In parallel, by collaborating with UCSF Cancer Center, we applied BAC array-based array CGH method to survey the copy number changes occurred in tumor DNAs. To c
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ompare the gene expression level with genomic loss and/or gain of each gene on the 11,000 cDNA chip, chromosome mapping of 11000 cDNAs was conducted by searching their nucleotide sequences against the UCSC genome browser databases. The data obtained were submitted to the public microarray databases NCBI GEO.
2) Integrated analyses of genomic and molecular signatures of neuroblastoma
We have finished array CGH analysis of 268 samples prepared from primary neuroblastomas and cell lines and compared the gene expression signatures and genomic aberrations such as chromosomal losses and gains. We could define the smallest region of overlaps of deletions at chromosome 1lq to be approximately 10 Mb, in which one gene exhibiting the differential expression between favorable and unfavorable neuroblastomas was identified. Therefore, we further performed quantitative real-time RT-PCR analysis of the gene by using multiple neuroblastoma RNA samples and also examined epigenetic modifications of its promoter region by bisulfite sequencing. Similar analysis was conducted for chromosome 1p36 region. Our next plan is to confirm the present results and do the functional analyses of the candidate genes that we have identified. Less
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