Summary of Research Project Results under JSPS FY2004
"Research for the Future Program"

1. Research Institution   The University of Tokyo
2. Research Area Life Sciences
3. Research Field Genome Research
4. Term of Project FY 2000 - FY 2004
5. Project Number 00L01402
6. Title of Project Systematic Expression Profile Analysis and its Application to Personalized Medicine

7. Project Leader

Name Institution,Department Title of Position
Yusuke, Nakamura The University of Tokyo ,The Institute of Medical Science Professor

8. Core Members

Names Institution,Department Title of Position
Satoru, Miyano The University of Tokyo, The Institute of Medical Science Professor
Youichi, Frukawa The University of Tokyo, The Institute of Medical Science Professor
Toyomasa, Katagiri The University of Tokyo, The Institute of Medical Science Associate Professor

9. Summary of Research Results

Through expression profile analysis using cDNA microarray of 32,000 human genes, have been analyzing genes whose expression was regulated by p53, and identified p53CSV1 (p53-inducible cell-survival factor) and STAG1; the former functions as a survival factor and the later functions as an apoptosis-inducing factor after DNA damage or other cellular stresses. We also identified and characterized molecules that can be applicable for development of diagnosis and/or treatment of cancer. The molecules identified and reported this years are RNF43(Ring Finger Protein 43)and LEMD1 (LEM domain containing1) for colon cancer, FZD10 for soft tissue sarcoma, HIG2 for kidney cancer, DDEFL1 (development and differentiation enhancing factor-like 1) and WDRPUH (WD40 repeat protein up-regulated in HCC) for liver cancer, SMYD3 (SET and MYND domain containing 3) and CLUAP1 (Clusterin Associated Protein 1)for liver and colon cancer, NALP7 (NACHT, leucine rich repeat and PYD containing 7) for seminoma, NOL8 (Nucleolar Protein 8)for diffuse-type gastric cancer, ADAM8(a disintegrin and metalloproteinase domain-8)for lung cancer, and RAB6KIFL and P-cadherin/CDH3 for pancreatic caner. We also applied cDNA microarray to establish a genetic method for predicting the outcome of chemotherapy, Iressa for lung cancer and the M-VAC treatment for bladder cancer. For Crohn disease (CD), an inflammatory bowel disease as characterized by chronic transmural, segmental and typically granulomatous inflammation of the gut, we have characterized two novel candidate gene loci associated with CD, SLC22A4 and SLC22A5 on chromosome 5 known as IBD5, and DLG5 on chromosome 10. Our findings imply significant differences in genetic background with CD susceptibility among different ethnic groups and further indicate some difficulty of population-based studies. For IgA nephropathy, the most common form of primary glomerulonephritis, we employed a large-scale, case-control association study using gene-based single-nucleotide polymorphism (SNP) markers, and identified a significant association between IgA nephropathy and a SNP located in the gene encoding immunoglobulin µ-binding protein 2 (IGHMBP2) at chromosome 11q13.2-q13.4 ( x 2=17.1, p=0.00003; odds ratio of 1.85 with 95% confidence interval of 1.39-2.50 in a dominant association model).

10. Key Words

( 1 ) cDNA microarray ( 2 ) cancer-specific antigen ( 3 ) molecular target
( 4 ) cancer vaccine ( 5 ) antibody ( 6 ) tumor marker
( 7 ) SNP ( 8 ) Crohn disease ( 9 ) IgA nephropathy