Molecular analysis of variety of genomic rearrangements and chimeric genes in tumorigenesis.

• Project/Area Number: 15K09486
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: TAKI TOMOHIKO 京都府立医科大学, 医学(系)研究科(研究院), 講師 (50322053)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: がん / ゲノム / キメラ遺伝子 / conjoined gene / エクソン / イントロン / RNAシーケンス / 悪性リンパ腫 / 白血病 / 遺伝子再構成

Outline of Final Research Achievements

We identified the conjoined genes and exonization of intron sequence in chimeric transcripts in hematologic malignancies. Conjoined gene is a chimeric transcript created with the genes adjacent each other, and the novel eleven conjoined genes were identified in a diffuse large B-cell lymphoma cell line in this study. Genome array analysis did not detect any copy number alterations in the regions of conjoined genes, suggesting the formation of fusion genes in transcriptional level. On the other hand, in chimeric transcripts created by chromosome translocation, some intronic sequences were inserted into chimeric transcripts occasionally, suggesting the exonization of intron by gene rearrangement in chromosomal translocations.

Research Products

• [Journal Article] Spontaneous remission of adult acute myeloid leukemia with t(8;16)(p11;p13)/MOZ-CBP fusion (2018)
  • Author(s): Hoshino T, Taki T, Takada S, Hatsumi N, Sakura T
  • Journal Title: Leuk Lymphoma Volume: 59 Issue: 1 Pages: 253-255
  • DOI: 10.1080/10428194.2017.1320712
  • Peer Reviewed
• [Journal Article] Prognostic impact of specific molecular profiles in pediatric acute megakaryoblastic leukemia in non-Down syndrome. (2017)
  • Author(s): Hara Y, Shiba N, Ohki K, Tabuchi K, Yamato G, Park MJ, Tomizawa D, Kinoshita K, Shimada A, Arakawa H, Saito AM, Kiyokawa N, Tawa A, Horibe K, Taga T, Adachi S, Taki T, and Hayashi Y.
  • Journal Title: Genes, Chromosomes & Cancer Volume: 14 February 2017 Issue: 5 Pages: 394-404
  • DOI: 10.1002/gcc.22444
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Molecular heterogeneity in APIP-FGFR2 fusion transcripts with diversity of genomic breakpoints in gastric cancer high-level amplifications at 11p13 and 10q26 (2017)
  • Author(s): Okuda T, Taki T, Nishida K Chinen Y, Nagoashi H, Sakakura C, Ohtsuji E, Taniwaki M
  • Journal Title: Oncol Lett Volume: 13 Issue: 1 Pages: 215-221
  • DOI: 10.3892/ol.2016.5386
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Long-term outcome of six-month maintenance chemotherapy for acute lymphoblastic leukemia in children. (2017)
  • Author(s): Kato M, Ishimaru S, Seki M, Yoshida K, Shiraishi Y, Chiba K, Kakiuchi N, Sato Y, Ueno H, Tanaka H, Inukai T, Tomizawa D, Hasegawa D, Osumi T, Arakawa Y, Aoki T, Okuya M, Kaizu K, Kato K, Taneyama Y, Goto H, Taki T, Takagi M, Sanada M, Koh K, Takita J, Miyano S, Ogawa S, Ohara A, Tsuchida M, Manabe A.
  • Journal Title: Leukemia. Volume: 31 Issue: 3 Pages: 580-584
  • DOI: 10.1038/leu.2016.274
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Preserved High Probability of Overall Survival with Significant Reduction of Chemotherapy for Myeloid Leukemia in Down Syndrome: A Nationwide Prospective Study in Japan. (2016)
  • Author(s): Taga T, Watanabe T, Tomizawa D, Kudo K, Kiminori Terui K, Moritake H, Kinoshita A, Iwamoto S, Nakayama H, Takahashi H, Shimada A MD, Taki T, Toki T, Ito E, Goto H, Koh K, Saito AM, Horibe K, Nakahata T, Tawa A, Adachi S.
  • Journal Title: Pediatr Blood Cancer Volume: 63 Issue: 2 Pages: 248-54
  • DOI: 10.1002/pbc.25789
  • Peer Reviewed
• [Journal Article] High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group. (2016)
  • Author(s): Takahashi H, Watanabe T, Kinoshita A, Yuza Y, Moritake H, Terui K, Iwamoto S, Nakayama H, Shimada A, Kudo K, Taki T, Yabe M, Matsushita H, Yamashita Y, Koike K, Ogawa A, Kosaka Y, Tomizawa D, Taga T, Saito AM, Horibe K, Nakahata T, Miyachi H, Tawa A, Adachi S.
  • Journal Title: Br J Haematol. Volume: 印刷中 Issue: 3 Pages: 437-443
  • DOI: 10.1111/bjh.14068
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CXCR4 overexpression is a poor prognostic factor in pediatric acute myeloid leukemia with low risk: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group (2016)
  • Author(s): Matsuo H, Nakamura N, Tomizawa D, Saito AM, Kiyokawa N, Horibe K, Nishinaka-Arai Y, Tokumasu M, Itoh H, Kamikubo Y, Nakayama H, Kinoshita A, Taga T, Tawa A, Taki T, Tanaka S, Adachi S
  • Journal Title: Pediatr Blood Cancer Volume: 63 Issue: 8 Pages: 1394-1399
  • DOI: 10.1002/pbc.26035
  • Peer Reviewed
• [Journal Article] Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan (2016)
  • Author(s): Imamura T, Kiyokawa N, Kato M, Imai C, Okamoto Y, Yano M, Ohki K, Yamashita Y, Kodama Y, Saito A, Mori M, Ishimaru S, Deguchi T, Hashii Y, Shimomura Y, Hori T, Kato K, Goto H, Ogawa C, Koh K, Taki T, Manabe A, Sato A, Kikuta A, Adachi S, Horibe K, Ohara A, Watanabe A, Kawano Y, Ishii E, Shimada H
  • Journal Title: Blood Cancer J Volume: 6 Issue: 5 Pages: e419-e419
  • DOI: 10.1038/bcj.2016.28
  • Peer Reviewed / Open Access
• [Journal Article] Genomic analysis of clonal origin of Langerhans cell histiocytosis following acute lymphoblastic leukemia (2015)
  • Author(s): 2.Kato M, Seki M, Yoshida K, Sato Y, Oyama R, Arakawa Y, Kishimoto H, Taki T, Akiyama M, Shiraishi Y, Chiba K, Tanaka H, Mitsuiki N, Kajiwara M, Mizutani S, Sanada M, Miyano S, Ogawa S, Koh K, Takita J.
  • Journal Title: British Journal of Haematology Volume: Nov 5 Issue: 1 Pages: 169-172
  • DOI: 10.1111/bjh.13841
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Unique clonal relationship between T-cell acute lymphoblastic leukemia and subsequent Langerhans cell histiocytosis with TCR rearrangement and NOTCH1 mutation. (2015)
  • Author(s): Yokokawa Y, Taki T, Akiyama M, Kobayashi S, Nagoshi H, Chinen Y, Morimoto A, Ida H, Taniwaki M.
  • Journal Title: Genes Chromosomes Cancer Volume: 54 Issue: 7 Pages: 409-417
  • DOI: 10.1002/gcc.22252
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Transient myeloproliferative disorder with partial trisomy 21. (2015)
  • Author(s): Takahashi T, Inoue A, Yoshimoto J, Kanamitsu K, Taki T, Imada M, Yamada M, Ninomiya S, Toki T, Terui K, Ito E, Shimada A.
  • Journal Title: Pediatr Blood Cancer Volume: 62 Issue: 11 Pages: 2021-2024
  • DOI: 10.1002/pbc.25624
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Transcriptional dysregulation of the deleted in colorectal carcinoma gene in multiple myeloma and monoclonal gammopathy of undetermined significance. (2015)
  • Author(s): Nagoshi H, Taki T, Chinen Y, Tatekawa S, Tsukamoto T, Maegawa S, Yamamoto-Sugitani M, Tsutsumi Y, Kobayashi T, Matsumoto Y, Horiike S, Okuno Y, Fujiwara S, Hata H, Kuroda J, Taniwaki M.
  • Journal Title: Genes Chromosomes Cancer Volume: 54 Issue: 12 Pages: 788-795
  • DOI: 10.1002/gcc.22290
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 「それぞれの癌」診断・治療の現状と展望．小児がんにおける分子診断の現状と課題 (2017)
  • Author(s): 滝 智彦
  • Organizer: 第55回日本癌治療学会学術集会
  • Invited
• [Presentation] 小児血液・がん領域のゲノム医療において考慮すべき遺伝医療の特性と課題．本セッション計画の背景について (2017)
  • Author(s): 滝 智彦
  • Organizer: 第59回日本小児血液・がん学会学術集会
  • Invited
• [Presentation] BCL11B短鎖バリアントは成人T細胞白血病・リンパ腫の発症に関与する (2017)
  • Author(s): Happy Permatasari, 中畑 新吾, 市川 朝永, 齋藤 祐介, 滝 智彦, 谷脇 雅史, 森下 和広
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] BCL11B短鎖バリアントは成人T細胞白血病・リンパ腫の発症に関与する (2017)
  • Author(s): Happy Permatasari, 中畑 新吾, 市川 朝永, 齋藤 祐介, 滝 智彦, 谷脇 雅史, 森下 和広
  • Organizer: 第79回日本血液学会学術集会
• [Presentation] Biology and Prognostic Markers in Young Children with Acute Myeloid Leukemia -the Jccg Study, JPLSG AML-05- (2017)
  • Author(s): Yusuke Hara, Norio Shiba, Genki Yamato, Jun Okubo, Kentaro Ohki, Myoung-Ja Park, Manabu Sotomatsu, Daisuke Tomizawa, Tomohiko Taki, Akitoshi Kinoshita, Nobutaka Kiyokawa, Takashi Taga, Hirokazu Arakawa, Akio Tawa, Keizo Horibe, Souichi Adachi, Yasuhide Hayashi
  • Organizer: 59th Annual Meeting of the American Society of Hematology
  • Int'l Joint Research
• [Presentation] Clinical Features and Prognostic Impact of RUNX1 and PTPN11 Mutations in Pediatric Acute Myeloid Leukemia―the Jccg Study, JPLSG AML-05- (2017)
  • Author(s): Genki Yamato, Norio Shiba, Kenichi Yoshida, Yusuke Hara, Kentaro Ohki, Jun Okubo, Myoung-Ja Park, Manabu Sotomatsu, Tomohiko Taki, Hirokazu Arakawa, Nobutaka Kiyokawa, Daisuke Tomizawa, Souichi Adachi, Takashi Taga, Keizo Horibe, Seishi Ogawa, Yasuhide Hayashi
  • Organizer: 59th Annual Meeting of the American Society of Hematology
  • Int'l Joint Research
• [Presentation] RNA Sequencing Illustrates the Genetic Backgrounds of Pediatric Acute Myeloid Leukemia (2017)
  • Author(s): Norio Shiba, Kenichi Yoshida, Yusuke Hara, Genki Yamato, Masashi Sanada, Yuichi Shiraishi, Kentaro Ohki, Jun Okubo, Myoung-JA PARK, Daisuke Tomizawa, Tomohiko Taki, Manabu Sotomatsu, Keizo Horibe, Takashi Taga, Souichi Adachi, Akio Tawa, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi
  • Organizer: 59th Annual Meeting of the American Society of Hematology
  • Int'l Joint Research
• [Presentation] Nationwide Survey of Pediatric Hypodiploid Acute Lymphoblastic Leukemia in Japan (2017)
  • Author(s): Ishimaru S, Okamoto Y, Imai C, Sakaguchi H, Taki T, Hasegawa D, Cho Y, Kakuda H, Sano H, Manabe A, Imamura T, Kato M, Arakawa Y, Shimonodan H, Sato A, Suenobu S, Inukai T, Watanabe A, Kawano Y, Kikuta A, Horibe K, Ohara A, Koh K
  • Organizer: 59th Annual Meeting of the American Society of Hematology
  • Int'l Joint Research
• [Presentation] 5q-核型異常を持つ小児急性骨髄性白血病の臨床的特徴と予後 (2016)
  • Author(s): 木下明俊, 滝 智彦, 林 泰秀, 渡邊智之, 宮地勇人, 松下弘道, 矢部みはる, 富澤大輔, 高橋浩之, 多和昭雄, 堀部敬三, 多賀 崇, 足立壯一
  • Organizer: 第58回日本小児血液・がん学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-15
• [Presentation] 乳児急性骨髄性白血病におけるMLL遺伝子再構成及びCBFA2T3-GLIS2による予後層別化 (2016)
  • Author(s): 原 勇介, 柴 徳生, 大木健太郎, 大和玄季, 朴 明子, 富澤大輔, 滝 智彦, 木下明俊, 清河信敬, 荒川浩一, 多和昭雄, 堀部敬三, 多賀 崇, 足立壮一, 林 泰秀
  • Organizer: 第58回日本小児血液・がん学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-15
• [Presentation] Comprehensive analysis of conjoined genes in a DLBCL cell line, KPUM-UH1 by RNA-Seq (2016)
  • Author(s): Yosuke Matsumoto, Tomohiko Taki, Yoshiaki Chinen, Ryuichi Sato, Hiroko Adachi, Shinsuke Mizutani, Hisao Nagoshi, Yuji Shimura, Mihoko Yoshida, Mio Sugitani-Yamamoto, Tsutomu Kobayashi, Junya Kuroda, Kazuho Shimura, Hiroto Kaneko, Masakazu Nakano, Shigeo Horiike, Yasuo Ohkawara, Kei Tashiro, Masafumi Taniwakii
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-14
• [Presentation] Molecular features and their clinical impact in infant acute myeloid leukemia (2016)
  • Author(s): Yusuke Hara, Norio Shiba, Kentaro Ohki, Genki Yamato, Myoung-Ja Park, Daisuke Tomizawa, Tomohiko Taki, Akitoshi Kinoshita, Hirokazu Arakawa, Akio Tawa, Keizo Horibe, Takashi Taga, Souichi Adachi, Yasuhide Hayashi
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-14
• [Presentation] 胃癌細胞株の高度増幅領域より同定した 新規融合遺伝子APIP-FGFR2におけるゲノム切断点の多様性 (2015)
  • Author(s): 奥田隆史、滝 智彦、西田一弘、 知念良顕、名越久朗、阪倉長平、谷脇雅史
  • Organizer: 日本人類遺伝学会第60回大会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-14
• [Presentation] Diversity of genomic breakpoints in novel fusion gene APIP-FGFR2 in a gastric cancer cell line (2015)
  • Author(s): Takashi Okuda, Tomohiko Taki, Kazuhiro Nishida, Yoshiaki Chinen, Hisao Nagoshi, Chouhei Sakakura, Masafumi Taniwaki
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08