|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1999 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1998 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1997 : ¥1,200,000 (Direct Cost : ¥1,200,000)
(1997) In spite of the development of clinical techniques, the prognoses of many cancers are still poor. Comparative genomic hybridization (CGH) is useful for identification of novel oncogenes and tumor suppressor genes involved in the carcinogenesis. 1) Biliary tract cancer ; CGH was performed on 30 fresh frozen tissues of gallbladder cancers. Chromosomal gain of 12p was associated with stage III and IV (P<0.05). Therefore, gain of 12p may be a potential prognostic factor of gallbladder cancers. 2) Ovarian cancer ; In order to find genetic changes in drug-resistant tumors, CGH was performed on 21 primary ovarian cancers and some cell lines. We found gains in chromosomal regions 1p, 1q and 19p, and losses in 2p and 15q to be related to the cisplatin-resistant phenotype. The cell lines which acquired the taxol-resistance had chromosomal gain of 7q where MDR gene was located. The amplification of MDR gene was confirmed by southern blot analysis. Present findings suggest that these chromo
somal gains and losses may be potential indicators for prediction of resistance in ovarian cancer patients before cisplatin- and/or taxol-based chemotherapy. 3) Neuroblastoma ; We performed CGH on 24 neuroblastomas and dual-color FISH to identify genetic aberrations associated with progressive neuroblastoma. A novel chromosomal gain at 1q21-q25 was found in all of progressive stage 4 neuroblastomas. Furthermore, by FISH analysis using cosmid clones, the 1q21-q25 gain was narrowed to 1q23. These results suggest that DNA amplification at 1q23 may play a role in the development of progressive neuroblastoma in advanced stage.
(1998) To clarify the biological characteristics of regressive and progressive neuroblastomas, CGH was performed on 67 patients with neuroblastomas. The CGH data of all regressive tumors (stage1-3 and 4s) revealed whole-chromosome aberrations of whole portion of chromosome. On the other hand, progressive tumors revealed chromosomal gains and losses on regional portion of chromosome. Our data suggest that neuroblastomas are classified into two biologically different groups, one of which displays progressive disease which displays progressive disease which has partial chromosomal changes, whereas the other mimics advanced stage 3/4 neuroblastoma but displays regressive disease which has whole chromosomal aberrations.
(1999) Recent advances in DNA microarray allow us genome-wide analysis of genetic alterations including DNA copy number changes, mutations, and gene expression in cancers. We tried to establish array-based CGH with high resolutions, high quantitative capability and sensitivity, and applied this novel powerful method to mapping the putative oncogenes in cancers. Our arrayed CGH showed quantitative analysis of DNA copy number in the range from 1 to 10,000 copies. We detected 10 copies of the gene per cell. We also performed gene expression monitoring of gastric cancer using microarray with 4,000 cDNAs of known genes and identified many kinds of genes that were specifically expressed in gastric cancer. Less