2006 Fiscal Year Final Research Report Summary
DNA methylation alterations and their relationship to genomic instability in gastrointestinal cancer
| Project/Area Number |
17591387
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Jichi Medical University (2006)
Hamamatsu University School of Medicine (2005) |
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Principal Investigator |
SUZUKI Koichi Jichi Medical University, School of Medicine, Surgery, Assistant professor, 医学部, 助教 (70332369)
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| Project Period (FY) |
2005 – 2006
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| Keywords | genetic alteration / epigenetic alteration / methylation / demethylation / aging / gastric cancer / colon cancer / carcinogenesis |
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| Research Abstract |
We studied the relationships between genetic and epigenetic alterations in gastrointestinal cancer by integrating DNA copy number changes determined by arbitrarily primed PCR (AP-PCR) with DNA methylation variations estimated by methylation-sensitive amplified fragment length polymorphism (MS-AFLP). We analyzed about 100 different chromosomal regions by AP-PCR and over 150 random CpG loci by MS-AFLP in human colon and gastric carcinomas. DNA hypomethylation and hypermethylation alterations distributed gradually and increased with cancer patient age, in contrast with the age-independent genomic alterations. Increased DNA hypomethylation and hypermethylation correlated with increased genomic damage, but only hypomethylation was highly significant in multivariate analyses. We conclude that age-dependent accumulation of DNA demethylation precedes diploidy loss in a significant subset of gastrointestinal cancers.
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