| Project/Area Number |
16K21284
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
General medical chemistry
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Chinen Yoshiaki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10757602)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | FISH法 / CDKN2A/B欠失 / B細胞性リンパ腫 / 染色体微小領域欠損 / CDKN2A / 難治性B細胞腫瘍 |
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| Outline of Final Research Achievements |
Chromosomal microdeletions frequently cause the loss of prognostically relevant tumor suppressor genes in B cell lymphomas (BCLs). However, the detection of minute deletions has been mostly impossible by conventional methods due to their low resolution. We developed a novel method designated here as amplified-FISH (AM-FISH), which enables the detection of chromosomal microdeletion shorter than 50 kb in BCLs. In the AM-FISH, the 31 kb Fluorescein isothiocyanate (FITC)-conjugated DNA probe encoding only CDKN2A gene was first hybridized with chromosome, and then, was labeled with Alexa Fluor 488-conjugated anti-FITC secondary antibody to help increase sensitivity. CDKN2A signals were equally identifiable by AM-FISH and conventional FISH, and AM-FISH could detect tumor cells with CDKN2A deletion even in the clinical sample contaminated with normal cells to some extent. AM-FISH is a highly sensitive, specific and easy method for the diagnoses of various types of chromosomal microdeletions.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、B細胞リンパ腫（BCL）の高度悪性化の誘因となるCDKN2A/2B遺伝子欠失症例が、簡便、迅速、安価にスクリーニング可能であることが示され、CDKN2A/2B遺伝子欠損をもつBCL患者群の予後予測や治療層別化など新たな治療戦略の構築に寄与するものと考えられた。また、診断・治療に染色体微小欠失の有無の鑑別が必要となるその他の疾患についても応用可能であり、血液悪性腫瘍以外の領域にも応用可能であることが示唆された。
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