2006 Fiscal Year Final Research Report Summary
Mechanism of cancer susceptibility associated with PCS (premature chromatid separation) genetic trait
| Project/Area Number |
16590261
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Human genetics
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
IKEUCHI Tatsuro Tokyo Medical and Dental University, Medical Research Institute, Assoc.Prof. (90041839)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Kohtaro Tokyo Medical and Dental University, Medical Research Institute, Director (40000971)
YOSHIDA mitsuaki Tokyo Medical and Dental University, Medical, National Institute of Radiological Sciences, Section Chief (60182789)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Keywords | Premature chromatid separation / PCS syndrome / Chromosomal instability / Aneuploid cells / BUB1B gene / Mitotic spindle checkpoint / Wilms tumor / Cancer prone genetic traait |
|---|
| Research Abstract |
1. The PCS (premature chromatid separation) syndrome was established as a clinical entity (OMIM#176430) on the basis of our experiences in 7 Japanese families, being recognized to be a cancer-prone genetic trait due to the impairment of mitotic spindle checkpoint, or to the decreased expression of BUB1B-endoding protein (BubR1).
2. The frequency of cells in PCS is the most important hallmark for diagnosis of PCS syndrome. Hypotonic treatment of cells at 37℃ for 20 min was found to be most suitable among the conditions tested for the detection of PCS in individuals with the homozygous or heterozygous for the PCS trait.
3. Chromosomal and DNA polymorphic marker studies revealed that the tumors developing in PCS patients had uniparental (paternal) disomy (UPD) specifically for chromosome 11, suggesting that the increased dosage of imprinted genes such as paternally expressed IGF2 was primarily involved in tumor development.
4. Molecular analysis of BUB1B (encoding BubR1 protein) was performed in 7 Japanese families with PCS syndrome. In all the families studied, monoallelic BUB1B mutations were found : a single-base deletion in 4 families, and a splice site mutation, a nonsence mutation, and a missene mutation in one family each. Further analysis of haplotypes in the secomd alleles, where no mutations were detected, is now in progress.
5. Lymphoblastoid cell lines (LCLs) and fibroblasts derived from the two PCS patients and a number of LCLs from heterozygous carriers were established and stored.
|
Research Products
(16 results)
-
-
-
-
-
[Journal Article] Two infants with homozygous premature chromatid separation trait.2006
Author(s)
Numabe, H., Ikeuchi, T., Kajii, T.,, Kusakawa, L, Kato, I., Kosugi, S.:
-
Journal Title
American Journal of Human Genetics 77
Pages: #807
Description
「研究成果報告書概要(和文)」より
-
[Journal Article] Monoallelic BUB1B mutations and defective mitotic-spindle Checkpoint in seven families with premature chromatid separtion (PCS) syndrome.2006
Author(s)
Matsuura, S., Matsumoto, Y., Morishima, K., Izumi, K., et al., Ikeuchi, T., Kajii, T.:
-
Journal Title
American Joutnal of Medical Genetics 140A
Pages: 358-367
Description
「研究成果報告書概要(和文)」より
-
[Journal Article] Two infants with homozygous premature chromatid separation trait2006
Author(s)
Numabe, H., Ikeuchi, T.., Kajii, T., Kusakawa, I., Kato, I., Kosugi, S.
-
Journal Title
American Journal of Human Genetics 77
Pages: #807
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Monoallelic BUB1B mutations and defective mitotic-spindle Checkpoint in seven families with premature chromatid Separation(PCS)syndrome2006
Author(s)
Matsuura, S., Matsumoto, Y., Morishima, K., Izumi, K., et al., Ikeuchi, T., Kajii, T.
-
Journal Title
American Journal of Medical Genetics 140A
Pages: 358-367
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Two modes of microsatellite instability in human cancer : differenttial connection of defective DNA mismatch repair to dinucleotide repeat instability2005
Author(s)
Oda, S., et al, Ikeuchi, T., Tsuzuki, T., Sekiguchi, M., Karran, P., Yoshida, M.A.
-
Journal Title
Nucleic Acids Research 33
Pages: 1628-1636
Description
「研究成果報告書概要(和文)」より
-
-
-
-
-
-
-
