| Project/Area Number |
22591045
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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 | Kyoto Prefectural University of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 多発性骨髄腫 / SKY / FISH / ゲノムアレイ / 遺伝子再構成 |
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| Research Abstract |
To elucidate pathophysiology of multiple myeloma (MM), we performed molecular dissection of the breakpoints at chromosomal 8q24 and 18q21 rearrangements using FISH, SKY, oligonucleotide array , and RT -PCR procedures. PVT1 rearrangements were detected in 7 (13.0%) of 54 MM patients and 5 (45.5 %) of 11 MM cell lines. Two novel chimeric genes were identified, PVT1-NBEA and PVT1-WWOX. The PVT1-NBEA chimera in which PVT1 exon 1 was fused to NBEA exon 2 and the PVT1-WWOX in which PVT1 exon 1 was fused to WWOX exon 9 were associated with the expression of abnormal NBEA and WWOX lacking their N-terminus, respectively.These findings suggest that PVT1 rearrangements may represent a novel molecular paradigm underlying the pathology of 8q24 rearrangement-positive multiple myeloma. On the other hand, our studies focusing on 18q21 identified abnormal DCC transcripts in which DCC exon 2 was fused to part of DCC intron 1 hence lacking exon 1 in 15 cell lines using bubble PCR for cDNA. Putative abnormal DCC protein lacks a part of N-terminus, suggesting that structural abnormalities of DCC play some roles in the development and progression of MM.
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