1998 Fiscal Year Final Research Report Summary
Deletion Mapping of Chromosomes in Malignant Lymphoma and Molecular Cloning of a Putative Novel Tumor Suppressor Gene from the Loci
| Project/Area Number |
09671104
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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 |
Hematology
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| Research Institution | Nagoya University |
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Principal Investigator |
KINOSHITA Tomohiro School of Medicine, Nagoya University Assistant Professor, 医学部, 助手 (60283446)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Hirokazu School of Medicine, Medical Staff, 医学部, 医員
MURATE Takashi School of Medicine, Assistant Professor, 医学部, 助教授 (30239537)
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| Project Period (FY) |
1997 – 1998
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| Keywords | MALIGNANT LYMPHOMA / TUMOR SUPPRESSOR GENE / LOH / WAF1 / B-CELL / YAC |
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| Research Abstract |
Allelic deletions have been thought to be indicators of the presence of tumor suppressor genes (TSGs). As indicated by this allelotype study using 39 highly informative microsatellite markers distributed among all autosomal chromosomes, frequent loss of heterozygosity (LOH) has been found at 6p in B-cell non-Hodgkin lymphoma. To identify the common deleted regions (CDRs), we performed fine deletion mapping using 26 highly polymorphic microsatellite markers on 6p. The most frequent LOH occurred at D6S1721, where 9 of 18 of the informative cases (50%) had allelic losses. Seventeen of 32 cases (53%) exhibited LOH at least at one locus on 6p. Ten of these 17 cases showed interstitial deletions, and their LOH patterns indicated two CDRs on 6p ; one between D6S1721 and D6S260 (at 6p23-24), the other between D6S265 and D6S291 (at 6p21). The genetic distance of both CDRs was 6 cM.The CDKN1A (p21) is reported to be located within the interval of the CDR at 6p21, but no mutation of the gene was found in these 32 patients. These data suggested that these two loci might harbor novel putative TSGs responsible for the pathogenesis of malignant lymphoma. We have constructed a contig of yeast artificial chromosome (YAC) clones spanning the most frequent CDR at 6p23-24. This YAC contig can be used for fine physical mapping of the region and cloning of the candidate TSGs.
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