2007 Fiscal Year Final Research Report Summary
Systemic Analysis of transcriptional network in cancer
| Project/Area Number |
16101006
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied genomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ABURATANI Hiroyuki The University of Tokyo, Research Center for Advanced Science and Technology, Professor (10202657)
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| Co-Investigator(Kenkyū-buntansha) |
TSUTSUMI Shuichi The University of Tokyo, Research Center for Advanced Science and Technology, Assistant Professor (30345152)
ISHIKAWA Shumpei The University of Tokyo, Department of Pathology, Assistant Professor (50418638)
MLDORIKAWA Yutaka The University of Teikyo, Mizonokuchi Hospital, Instructor (10292905)
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| Project Period (FY) |
2004 – 2007
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| Keywords | genome / transcription / copy number variation / tiling array / DNA methylation / Chromatin immunoprecipitation |
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| Research Abstract |
To systemically elucidate the aberrant transcriptional regulation in cancer, we applied genomic technologies such as SNP typing array and genome tiling array.
1) Copy number analysis
We developed a novel algorithm, Genome Imbalance Map (GIM), for allelic copy number analysis of SNP genotyping assay data (Ishikawa, 2005), which can efficiently detect loss of heterozygosity and uniparental disomy. In particular, as it can discriminate the signal difference by one copy, it can identify a homozygous deletion in surgically resected cancer specimens, which are often contaminated with normal cells significantly. We identified homozygous deletion of CSMD1 gene at 8p23 locus in hepatocellular carcinoma. GIM algorithm was further developed and applied to generate the first generation Copy number variation map for human genome (Redon, Ishikawa, Nature, 2006).
2) DNA methylation analysis
DNA methylation is the important process for gene silencing. We used genome tiling array to comprehensively detect DNA methylation. Methylated DNA fragments were captured with anti-methyl cytosine antibody and detected on the genomic tiling array. Instead of PCR amplification, in vitro transcription was used to amplify the captured DNA with high reproducibility (Hayashi 2007). We observed that distribution of DNA methylation and histone acetylation is mutually exclusive.
3) Transcriptional network analysis
Co-expression network analysis was successfully applied on gene expression profile data to identify the activated pathway (Aggarwal 2006). Furthermore, to reveal the direct target genes in transcriptional cascades, we applied genome tiling array to detect the transcription factor binding sites (Kaneshiro 2007). We discovered co-localization of CTCF and cohesin, indicating the role of cohesin in chromatin loop formation (Wendt, Nature 2008).
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