Development of novel diagnostic and therapeutic approach for the diffuse large B cell lymphoma with CDKN2A deletion
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 |
Research Field |
Hematology
General medical chemistry
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
Chinen Yoshiaki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10757602)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
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 |
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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Report
(4 results)
Research Products
(13 results)
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[Journal Article] A novel method of amplified fluorescent in situ hybridization for detection of chromosomal microdeletions in B cell lymphoma.2019
Author(s)
Mizuno Y, Chinen Y, Tsukamoto T, Takimoto-Shimomura T, Matsumura-Kimoto Y, Fujibayashi Y, Kuwahara-Ota S, Fujino T, Nishiyama D, Shimura Y, Kobayashi T, Horiike S, Taniwaki M, Kuroda J.
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Journal Title
Int J Hematol.
Volume: 109
Issue: 5
Pages: 593-602
DOI
Related Report
Peer Reviewed
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[Journal Article] A novel method of amplified fluorescent in situ hybridization for detection of chromosomal microdeletions in B cell lymphoma2019
Author(s)
Mizuno Y, Chinen Y, Tsukamoto T, Takimoto-Shimomura T, Matsumura-Kimoto Y, Fujibayashi Y, Kuwahara-Ota S, Fujino T, Nishiyama D, Shimura Y, Kobayashi T, Horiike S, Taniwaki M, Kuroda J
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Journal Title
International Journal of Hematology
Volume: -
Related Report
Peer Reviewed
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[Journal Article] Prognostic impact of a past or synchronous second cancer in diffuse large B cell lymphoma.2018
Author(s)
Tanba K, Chinen Y, Uchiyama H, Uoshima N, Shimura K, Fuchida S, Kiyota M, Nakao M, Shimura Y, Kobayashi T, Horiike S, Wada K, Shimazaki C, Kaneko H, Kobayashi Y, Taniwaki M, Kuroda J.
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Journal Title
Blood Cancer J.
Volume: 8
Issue: 1
Pages: 1-5
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic impact of a past or synchronous second cancer in diffuse large B cell lymphoma2018
Author(s)
Kazuna Tanba, Yoshiaki Chinen, Hitoji Uchiyama, Nobuhiko Uoshima, Kazuho Shimura, Shinichi Fuchida, Miki Kiyota, Mitsushige Nakao, Yuji Shimura, Tsutomu Kobayashi, Shigeo Horiike, Katsuya Wada, Chihiro Shimazaki, Hiroto Kaneko, Yutaka Kobayashi, Masafumi Taniwaki, Junya Kuroda
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Journal Title
Blood Cancer Journal
Volume: 1
Pages: 1-1
Related Report
Peer Reviewed / Open Access
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[Journal Article] Epigenetic repression of miR-375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma.2017
Author(s)
Tatekawa S, Chinen Y, Ri M, Narita T, Shimura Y, Matsumura-Kimoto Y, Tsukamoto T, Kobayashi T, Kawata E, Uoshima N, Taki T, Taniwaki M, Handa H, Iida S, Kuroda J.
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Journal Title
British Journal of Haematology
Volume: 印刷中
Issue: 4
Pages: 534-546
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Cyclin D1 transcript variant in mantle cell lymphoma and myeloma with chromosome 11q13 abnormality2017
Author(s)
Yoshiaki Chinen, Taku Tsukamoto, Yayoi Kimoto, Tomoko Takimoto, Yoshimi Mizuno, Saori Maegata, Saeko Ota, Kazuna Tanba, Yuji Shimura, Tsutomu Kobayashi, Shigeo Horiike, Junya Kuroda
Organizer
第79回日本血液学会総会
Related Report
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[Presentation] Prognostic Impact of Past History of Other Malignancies in Diffuse Large B Cell Lymphoma2017
Author(s)
Kazuna Tanba, Yoshiaki Chinen, Hitoji Uchiyama, Nobuhiko Uoshima, Kazuho Shimura, Shin-ichi Fuchida, Miki Kiyota, Mitsushige Nakao, Yuji Shimura, Tsutomu Kobayashi, Shigeo Horiike, Katsuya Wada, Chihiro Shimazaki, Hiroto Kaneko, Yutaka Kobayashi, Masafumi Taniwaki, Junya Kuroda
Organizer
American society of Hematology, 59th Annual Meeting and Exposition
Related Report
Int'l Joint Research
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[Presentation] The Abnormal Repression of Mir-375 Expression By Overlapping Epigenetic Dysregulations in Myelomas2016
Author(s)
Shotaro Tatekawa, Yoshiaki Chinen, Yuji Shimura, Yayoi Matsumura-Kimoto, Hisao Nagoshi, Tsutomu Kobayashi, Eri Kawata, Tomoko Narita, Masaki Ri, Hiroshi Handa, Nobuhiko Uoshima, Shinsuke Iida, Junya Kuroda
Organizer
American society of Hematology, 58th Annual Meeting and Exposition
Place of Presentation
San Diego (USA)
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] Novel tumor-specific CCND1 isoforms in mantle cell lymphoma and myeloma with 11q23 abnormality2016
Author(s)
Yoshiaki Chinen, Shotaro Tatekawa, Saori Maegawa, Tomoko Takimoto, Hisao Nagoshi, Yuji Shimura, Mio Yamamoto-Sugitani, Tustomu Kobayashi, Shigeo Horiike, Masafumi Taniwaki, Junya Kuroda
Organizer
第78回日本血液学会学術集会
Place of Presentation
パシフィコ横浜(神奈川県横浜市)
Year and Date
2016-10-13
Related Report
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[Presentation] The epigenetic dysregulation of miR-375 for PDPK1 overexpression/activation in multiple myeloma2016
Author(s)
Shotaro Tatekawa, Yoshiaki Chinen, Yuji Shimura, Yayoi Matsumura-Kimoto, Hisao Nagoshi, Tsutomu Kobayashi, Eri Kawata, Tomoko Narita, Masaki Ri, Hiroshi Handa, Nobuhiko Uoshima, Shinsuke Iida, Junya Kuroda
Organizer
第78回日本血液学会学術集会
Place of Presentation
パシフィコ横浜(神奈川県横浜市)
Year and Date
2016-10-13
Related Report
-
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[Presentation] The epigenetic dysregulation of miR-375 for PDPK1 overexpression/activation in multiple myeloma2016
Author(s)
Shotaro Tatekawa, Yoshiaki Chinen, Yuji Shimura, Hisao Nagoshi, Tutor Kobayashi, Yayoi Kimoto, Eri Kawata, Tomoko Narita, Masaki Ri, Hiroshi Handa, Nobuhiko Uoshima, Shinsuke Iida, Junya Kuroda
Organizer
第41回日本骨髄腫学会学術集会
Place of Presentation
あわぎんホール(徳島県徳島市)
Year and Date
2016-05-28
Related Report