| Project/Area Number |
11138265
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (A)
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| Allocation Type | Single-year Grants |
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| Research Institution | National Cancer Center Resaerch Institute Carcinogenesis |
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Principal Investigator |
USHIJIMA Toshikazu National Cancer Center Res.Inst.Chief, 部長 (90232818)
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| Co-Investigator(Kenkyū-buntansha) |
ASADA Kiyoshi National Cancer Center Res.Inst.Staff Scientist, 研究員 (50311410)
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| Project Period (FY) |
1999
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1999: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | CpG island / DNA methylation / MS-RDA / Breast cancer / BRCA1 / G protein / Maintenance / Methylation instability |
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| Research Abstract |
The number and distribution of aberrant methylations in human breast cancers were investigated using a genome-wide scanning technique of aberrant methylations, methylation-sensitive-representational difference analysis (MS-RDA). MS-RDA of two human breast cancers revealed 25 hypermethylated DNA fragments and 22 hypomethylated DNA fragments. Prevalences of these aberrant methylations were examined using a total of 14 breast cancers. Five cancers showed high incidence of aberrant hyper- and hypomethylations, two showed high incidence of only aberrant hypomethylations, and the remaining seven showed limited number of aberrant methylations. These findings indicated that a subset of human breast cancers shows higher rate of occurrence of aberrant methylations than the others. To explore the underlying molecular abnormality for the "methylation instability", germline mutations of BRCA1 were analyzed in the 14 cases, but there was no correlation between the "methylation instability" and BRCA1 germline mutations. On the other hand, we identified a G-protein subunit and a cytoplasmic second messenger as genes that are hypermethylated and transcriptionally repressed in more than half of human breast cancers.
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