大規模シーケンスとコンピューティングによるがんの進化と多様性の解明

2017 Fiscal Year Annual Research Report

• Project Area: Conquering cancer through neo-dimensional systems understanding
• Project/Area Number: 15H05909
• Research Institution: Kyoto University
• Principal Investigator: 小川 誠司 京都大学, 医学研究科, 教授 (60292900)
• Co-Investigator(Kenkyū-buntansha): 南谷 泰仁 京都大学, 医学研究科, 特定准教授 (60451811) ; 牧島 秀樹 京都大学, 医学研究科, 講師 (40402127) ; 江藤 浩之 京都大学, iPS細胞研究所, 教授 (50286986) [Withdrawn]
• Project Period (FY): 2015-06-29 – 2020-03-31
• Keywords: RNAシーケンス / ゲノム科学 / システムゲノム科学 / 腫瘍学

Outline of Annual Research Achievements

a)癌の起源と進化に関する解析:食道癌(ESCC)患者および健常者より多数の微小(4mm2～0.2mm2)サンプリングによる次世代シーケンス解析を行ったところ、腫瘍組織のみならず健常人正常食道上皮においてもESCCで認められるドライバー遺伝子の変異を有するクローンが加齢に伴って全ての被験者で生じていること、またそれらはアルコールや喫煙によって促進されることが明らかとなった。
b)全ゲノムシーケンスによる新たな発がんメカニズムの解析:Down症候群に伴う急性巨核芽球性白血病(AMKL)の全ゲノムシーケンスの解析により、RUNX1遺伝子において新規なtandem duplication が本病型に特異的かつ極めて高頻度(～60%)に生じていることが明らかとなった。また、中枢神経リンパ腫およびMDS/AML計320例について全ゲノムシーケンスを行った。
c)胚細胞変異の解析:日本骨髄バンクのMDSの保存試料約800例および本事業で集積されたに日本人MDS 700試料について、骨髄腫瘍の発症に関わる胚細胞変異の種類と頻度を解析した。その結果、DDX41 の新たなリスクアレル(ないし候補)XX個が同定された。また、驚くべきことにDDX41の胚細胞変異は、我が国における孤発性高リスクMDSの7～8%もの頻度で認められ、MDSの発症には胚細胞変異が極めて大きな役割を担っていることが明らかとなった。
d)臨床シーケンスに関する検討: StageII/IIIの大腸癌検体2000例について既知のドライバー変異に関するターゲットシーケンスを行い、POLE変異を有する大腸がんが他の大腸がんと比較して特徴的な遺伝子変異プロフアイルを有すること、また有意に転移が少なく予後良好であること、従って予後予測の優れたバイオマーカーとなることが明らかとなった。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

a)癌の起源と進化に関する解析:健常食道上皮の網羅的な変異解析によって、食道がんで認められるドライバー変異が加齢によって全ての患者で生じていることが明らかとなった。このことは、食道がんの基盤となる初期の変化は全ての個体で生じている普遍的な現象であって、食道がんの起源の解明に関して予想以上の大きな進展が認められた。また、尿路上皮についても同様の知見が得られつつある。
b)全ゲノムシーケンスについても当初予定していた200例の解析を上回る試料(320試料)の解析が終了した。Non-coding領域のドライバー変異の検出感度を高める目的で、本年度はMDS/AMLに特化して解析を行った結果リンパ腫の解析については、中枢神経リンパ腫を除き、解析の遅延が生じている。
c)胚細胞変異の解析では、DDX41の新規胚細胞リスクアレルが同定されるとともに、これらのリスクアレルが孤発性高リスクMDSの7～8%もの症例で生じていることを見いだした。本発見は、少なくとも我が国においては、胚細胞変異が、従来考えられている以上にMDSの発症に深く関わっていることを示すもので、大きな成果と考えている。
d)一方、大腸がんの標的シーケンスに関しては、当初予定していた症例数を大きく上回る2000例の解析を実施した。また、これらの解析から、POLE変異を有する大腸がんが遺伝学的、臨床的に特徴的な一群を構成していることを明らかにした。
以上より、一部の項目を除き、年度当初に予定していた解析は概ね順調に進捗しており、また一部の解析では、当初の予測を上回る成果が得られていることから、研究は概ね順調に振興していると判断している。

Strategy for Future Research Activity

a)癌の起源と進化に関する解析。食道癌、乳がん、および泌尿器系腫瘍(腎盂尿管癌)について、前がん病変、健常組織を含めた多数サンプリングを行い、全エクソンシーケンスを行うことにより、遺伝子変異の観点から、これらのがんの初期発生とクローン進化の過程を解明する。 b)全ゲノムシーケンスによる新たな発がんメカニズムの解析。骨髄異形成症候群(MDS)および急性骨髄性白血病(AML)については計400～500例、また成人T細胞白血病(ATL)、尿路上皮がん、南部人種、B細胞リンパ腫についても、追加解析を行う。
c)正常組織におけるクローン拡大の解析。がんの発症の初期過程におけるクローン選択を明らかにする目的で、尿路上皮がん、乳がん、食道がんについて、担がん患者の尿管、乳腺上皮食道上皮の高密度サンプリングにより採取した健常組織について、全エクソンシーケンスを行い、健常組織に生ずるクローン拡大を明らかにすることにより、がんの初期発症過程を解明する。また、潰瘍性大腸炎についても同様の解析を行い、炎症による初期のクローン選択のメカニズムの解明を行う。
d)単一細胞シーケンス技術の開発。遺伝子変異と遺伝子発現の同時測定を可能とする単一細胞シーケンス技術を開発する。 e)胚細胞系列の変異に関する解析。AML/MDSおよび健常日本人集団における主要なDDX41変異アレルの頻度を測定・比較することにより、これらの変異アレルのAML/MDS発症における相対リスクを明らかにする。
f)臨床シーケンスに関する検討。大腸がんについて、昨年度同定したPOLE変異を有する特徴的な一群について、さらに症例を追加し、POLE変異大腸がんのゲノムプロファイルと臨床像を明らかにする。その過程でえられる1800例の大腸がんの変異データに基づいて、ドライバー変異に基づく大腸がんの分子分類の構築を試みる。

Research Products

• [Journal Article] Diagnosis and relapse: cytogenetically normal acute myelogenous leukemia without FLT3-ITD or MLL-PTD (2017)
  • Author(s): Chien W., Sun Q. Y., Ding L. W., Mayakonda A., Takao S., Liu L., Lim S. L., Tan K. T., Garg M., De Sousa Maria Varela A., Xiao J., Jacob N., Behrens K., Stocking C., Lill M., Madan V., Hattori N., Gery S., Ogawa S., Wakita S., Ikezoe T., Shih L. Y., Alpermann T., Haferlach T., Yang H., Koeffler H. P.
  • Journal Title: Leukemia Volume: 31 Pages: 762-766
  • DOI: 10.1038/leu.2016.343
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clonal evolution in myelodysplastic syndromes (2017)
  • Author(s): da Silva-Coelho P, et al.
  • Journal Title: Nature communications Volume: 8 Pages: 15099
  • DOI: 10.1038/ncomms15099
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia (2017)
  • Author(s): Ding L. W., Sun Q. Y, st al.
  • Journal Title: Cancer research Volume: 77 Pages: 390-400
  • DOI: 10.1158/0008-5472.CAN-16-1303
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma (2017)
  • Author(s): Fujisawa M., Sakata-Yanagimoto M., Nishizawa S., Komori D., Gershon P., Kiryu M., Tanzima S., Fukumoto K., Enami T., Muratani M., Yoshida K., Ogawa S., Matsue K., Nakamura N., Takeuchi K., Izutsu K., Fujimoto K., Teshima T., Miyoshi H., Gaulard P., Ohshima K., Chiba S.
  • Journal Title: Leukemia Volume: 32 Pages: 694-702
  • DOI: 10.1038/leu.2017.273
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel lincRNA SLINKY is a prognostic biomarker in kidney cancer (2017)
  • Author(s): Gong X., Siprashvili Z., Eminaga O., Shen Z., Sato Y., Kume H., Homma Y., Ogawa S., Khavari P. A., Pollack J. R., Brooks J. D.
  • Journal Title: Oncotarget Volume: 8 Pages: 18657-18669
  • DOI: 10.18632/oncotarget.15703
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Constitutional abnormalities of IDH1 combined with secondary mutations predispose a patient with Maffucci syndrome to acute lymphoblastic leukemia (2017)
  • Author(s): Hirabayashi S., Seki M., Hasegawa D., Kato M., Hyakuna N., Shuo T., Kimura S., Yoshida K., Kataoka K., Fujii Y., Shiraishi Y., Chiba K., Tanaka H., Kiyokawa N., Miyano S., Ogawa S., Takita J., Manabe A.
  • Journal Title: Pediatr Blood Cancer Volume: 64 Pages: e26647
  • DOI: 10.1002/pbc.26647
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular studies reveal MLL-MLLT10/AF10 and ARID5B-MLL gene fusions displaced in a case of infantile acute lymphoblastic leukemia with complex karyotype (2017)
  • Author(s): Hiwatari M., Seki M., Akahoshi S., Yoshida K., Miyano S., Shiraishi Y., Tanaka H., Chiba K., Ogawa S., Takita J.
  • Journal Title: Oncol Lett Volume: 14 Pages: 2295-2299
  • DOI: 10.3892/ol.2017.6430
  • Peer Reviewed / Open Access
• [Journal Article] Recurrent genetic defects on chromosome 5q in myeloid neoplasms (2017)
  • Author(s): Hosono N., Makishima H., Mahfouz R., Przychodzen B., Yoshida K., Jerez A., LaFramboise T., Polprasert C., Clemente M. J., Shiraishi Y., Chiba K., Tanaka H., Miyano S., Sanada M., Cui E., Verma A. K., McDevitt M. A., List A. F., Saunthararajah Y., Sekeres M. A., Boultwood J., Ogawa S., Maciejewski J. P.
  • Journal Title: Oncotarget Volume: 8 Pages: 6483-6495
  • DOI: 10.18632/oncotarget.14130
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hypoxic adaptation of leukemic cells infiltrating the CNS affords a therapeutic strategy targeting VEGFA (2017)
  • Author(s): Kato I., Nishinaka Y., Nakamura M., Akarca A. U., Niwa A., Ozawa H., Yoshida K., Mori M., Wang D., Morita M., Ueno H., Shiozawa Y., Shiraishi Y., Miyano S., Gupta R., Umeda K., Watanabe K., Koh K., Adachi S., Heike T., Saito M. K., Sanada M., Ogawa S., Marafioti T., Watanabe A., Nakahata T., Enver T.
  • Journal Title: Blood Volume: 129 Pages: 3126-3129
  • DOI: 10.1182/blood-2016-06-721712
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children (2017)
  • Author(s): Kato M., et al.
  • Journal Title: Leukemia Volume: 31 Pages: 580-584
  • DOI: 10.1038/leu.2016.274
  • Peer Reviewed
• [Journal Article] Dynamics of clonal evolution in myelodysplastic syndromes (2017)
  • Author(s): Makishima H., et al.
  • Journal Title: Nature genetics Volume: 49 Pages: 204-212
  • DOI: 10.1038/ng.3742
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical significance of somatic mutation in unexplained blood cytopenia (2017)
  • Author(s): Malcovati L., Galli A., Travaglino E., Ambaglio I., Rizzo E., Molteni E., Elena C., Ferretti V. V., Catricala S., Bono E., Todisco G., Bianchessi A., Rumi E., Zibellini S., Pietra D., Boveri E., Camaschella C., Toniolo D., Papaemmanuil E., Ogawa S., Cazzola M.
  • Journal Title: Blood Volume: 129 Pages: 3371-3378
  • DOI: 10.1182/blood-2017-01-763425
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Structural Determinants of the Gain-of-Function Phenotype of Human Leukemia-associated Mutant CBL Oncogene (2017)
  • Author(s): Nadeau S. A., An W., Mohapatra B. C., Mushtaq I., Bielecki T. A., Luan H., Zutshi N., Ahmad G., Storck M. D., Sanada M., Ogawa S., Band V., Band H.
  • Journal Title: J Biol Chem Volume: 292 Pages: 3666-3682
  • DOI: 10.1074/jbc.M116.772723
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Acquired expression of CblQ367P in mice induces dysplastic myelopoiesis mimicking chronic myelomonocytic leukemia (2017)
  • Author(s): Nakata Y., Ueda T., Nagamachi A., Yamasaki N., Ikeda K. I., Sera Y., Takubo K., Kanai A., Oda H., Sanada M., Ogawa S., Tsuji K., Ebihara Y., Wolff L., Honda Z. I., Suda T., Inaba T., Honda H.
  • Journal Title: Blood Volume: 129 Pages: 2148-2160
  • Peer Reviewed
• [Journal Article] Identification of cell-type-specific mutations in nodal T-cell lymphomas (2017)
  • Author(s): Nguyen T. B., Sakata-Yanagimoto M., Asabe Y., Matsubara D., Kano J., Yoshida K., Shiraishi Y., Chiba K., Tanaka H., Miyano S., Izutsu K., Nakamura N., Takeuchi K., Miyoshi H., Ohshima K., Minowa T., Ogawa S., Noguchi M., Chiba S.
  • Journal Title: Blood cancer journal Volume: 7 Pages: e516
  • DOI: 10.1038/bcj.2016.122
  • Peer Reviewed / Open Access
• [Journal Article] BCL6 locus is hypermethylated in angioimmunoblastic T-cell lymphoma (2017)
  • Author(s): Nishizawa S., Sakata-Yanagimoto M., Hattori K., Muto H., Nguyen T., Izutsu K., Yoshida K., Ogawa S., Nakamura N., Chiba S.
  • Journal Title: International journal of hematology Volume: 105 Pages: 465-8211;469
  • DOI: 10.1007/s12185-016-2159-z
  • Peer Reviewed / Open Access
• [Journal Article] Blastic transformation of juvenile myelomonocytic leukemia caused by the copy number gain of oncogenic KRAS (2017)
  • Author(s): Osumi T., Kato M., Ouchi-Uchiyama M., Tomizawa D., Kataoka K., Fujii Y., Seki M., Takita J., Ogawa S., Uchiyama T., Ohki K., Kiyokawa N.
  • Journal Title: Pediatr Blood Cancer Volume: 64 Pages: e26496
  • DOI: 10.1002/pbc.26469
  • Peer Reviewed / Open Access
• [Journal Article] Genomic determinants of chronic myelomonocytic leukemia (2017)
  • Author(s): Patel B. J., Przychodzen B., Thota S., Radivoyevitch T., Visconte V., Kuzmanovic T., Clemente M., Hirsch C., Morawski A., Souaid R., Saygin C., Nazha A., Demarest B., LaFramboise T., Sakaguchi H., Kojima S., Carraway H. E., Ogawa S., Makishima H., Sekeres M. A., Maciejewski J. P.
  • Journal Title: Leukemia Volume: 31 Pages: 2815-8211;2823
  • DOI: 10.1038/leu.2017.164
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia (2017)
  • Author(s): Seki M., et al.
  • Journal Title: Nature genetics Volume: 49 Pages: 1274-1281
  • DOI: 10.1038/ng.3900
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Significance of perivascular tumour cells defined by CD109 expression in progression of glioma (2017)
  • Author(s): Shiraki Y., Mii S., Enomoto A., Momota H., Han Y. P., Kato T., Ushida K., Kato A., Asai N., Murakumo Y., Aoki K., Suzuki H., Ohka F., Wakabayashi T., Todo T., Ogawa S., Natsume A., Takahashi M.
  • Journal Title: J Pathol Volume: 243 Pages: 468-480
  • DOI: 10.1002/path.4981
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD) (2017)
  • Author(s): Sun Q. Y., et al.
  • Journal Title: Leukemia Volume: 31 Pages: 1-8211;10
  • DOI: 10.1038/leu.2016.160
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] BRCA1 alterations with additional defects in DNA damage response genes may confer chemoresistance to BRCA-like breast cancers treated with neoadjuvant chemotherapy (2017)
  • Author(s): Takada M., Nagai S., Haruta M., Sugino R. P., Tozuka K., Takei H., Ohkubo F., Inoue K., Kurosumi M., Miyazaki M., Sato-Otsubo A., Sato Y., Ogawa S., Kaneko Y.
  • Journal Title: Genes Chromosomes Cancer Volume: 56 Pages: 405-420
  • Peer Reviewed / Open Access
• [Journal Article] A TLR3-Specific Adjuvant Relieves Innate Resistance to PD-L1 Blockade without Cytokine Toxicity in Tumor Vaccine Immunotherapy (2017)
  • Author(s): Takeda Y., Kataoka K., Yamagishi J., Ogawa S., Seya T., Matsumoto M.
  • Journal Title: Cell Rep Volume: 19 Pages: 1874-8211;1887
  • DOI: 10.1016/j.celrep.2017.05.015
  • Peer Reviewed / Open Access
• [Journal Article] Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia (2017)
  • Author(s): Togasaki E., et al.
  • Journal Title: Blood cancer journal Volume: 7 Pages: e559
  • DOI: 10.1038/bcj.2017.36
  • Peer Reviewed / Open Access
• [Journal Article] Copy number analysis identifies tumor suppressive lncRNAs in human osteosarcoma (2017)
  • Author(s): Xie J., Lin D., Lee D. H., Akunowicz J., Hansen M., Miller C., Sanada M., Kato M., Akagi T., Kawamata N., Ogawa S., Koeffler H. P.
  • Journal Title: Int J Oncol Volume: 50 Pages: 863-872
  • DOI: 10.3892/ijo.2017.3864
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] ASXL2 mutations are frequently found in pediatric AML patients with t(8;21)/ RUNX1-RUNX1T1 and associated with a better prognosis (2017)
  • Author(s): Yamato G., Shiba N., Yoshida K., Shiraishi Y., Hara Y., Ohki K., Okubo J., Okuno H., Chiba K., Tanaka H., Kinoshita A., Moritake H., Kiyokawa N., Tomizawa D., Park M. J., Sotomatsu M., Taga T., Adachi S., Tawa A., Horibe K., Arakawa H., Miyano S., Ogawa S., Hayashi Y.
  • Journal Title: Genes Chromosomes Cancer Volume: 56 Pages: 382-393
  • DOI: 10.1002/gcc.22443
  • Peer Reviewed / Open Access
• [Journal Article] The U2AF1S34F mutation induces lineage-specific splicing alterations in myelodysplastic syndromes (2017)
  • Author(s): Yip B. H., Steeples V., Repapi E., Armstrong R. N., Llorian M., Roy S., Shaw J., Dolatshad H., Taylor S., Verma A., Bartenstein M., Vyas P., Cross N. C., Malcovati L., Cazzola M., Hellstrom-Lindberg E., Ogawa S., Smith C. W., Pellagatti A., Boultwood J.
  • Journal Title: The Journal of clinical investigation Volume: 127 Pages: 2206-2221
  • DOI: 10.1172/JCI91363
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Metachronous anaplastic sarcoma of the kidney and thyroid follicular carcinoma as manifestations of DICER1 abnormalities (2017)
  • Author(s): Yoshida M., Hamanoue S., Seki M., Tanaka M., Yoshida K., Goto H., Ogawa S., Takita J., Tanaka Y.
  • Journal Title: Human pathology Volume: 61 Pages: 205-209
  • DOI: 10.1016/j.humpath.2016.06.024
  • Peer Reviewed
• [Journal Article] Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation (2017)
  • Author(s): Yoshizato T., et al.
  • Journal Title: Blood Volume: 129 Pages: 2347-2358
  • DOI: 10.1182/blood-2016-12-754796
  • Peer Reviewed
• [Journal Article] Origins of myelodysplastic syndromes after aplastic anemia. (2017)
  • Author(s): Negoro E., Nagata Y., Clemente MJ., Hosono N., Shen W., Nazha A., Yoshizato T., Hirsch C., Przychodzen B., Mahfouz RZ., Kuzmanovic T., Sekeres MA., Makishima H., Ogawa S., Maciejewski JP.
  • Journal Title: Blood Volume: 130 Pages: 1953-1957
  • DOI: 10.1182/blood-2017-02-767731
  • Peer Reviewed
• [Presentation] A Novel Genetic Mechanism of Evading Anti-tumor Immunity In Multiple Human Cancers (2017)
  • Author(s): Seishi Ogawa
  • Organizer: 2017 AACR Annual Meeting
  • Int'l Joint Research / Invited
• [Presentation] Landscape of driver gene mutations in stage II and stage III colorectal cancer (2017)
  • Author(s): Yoshikage Inoue, Nobuyuki Kakiuchi, Kenichi Yoshida, Yusuke Shiozawa, Yasuhide Takeuchi, Yuichi Shiraishi, Kenichi Chiba, Keisuke Kataoka, Hiroko Tanaka, Ai Okada, Satoru Miyano, Masashi Ueno, Satoshi Nagayama, Yoshiharu Sakai, Seishi Ogawa
  • Organizer: 2017 AACR Annual Meeting
  • Int'l Joint Research
• [Presentation] Genomic Landscape and Clonal Expansions of Upper Urinary Tract Urothelial Carcinoma (2017)
  • Author(s): Yoichi Fujii1, Yusuke Sato2, Shigekatsu Maekawa2, Hiromichi Suzuki1, Tetsuichi Yoshizato1, Kenichi Yoshida1, Yuichi Shiraishi3, Kenichi Chiba3, Hiroko Tanaka3, Tohru Nakagawa2, Haruki Kume2, Hiroaki Nishimatsu4, Yoshikazu Hirano4, Masashi Sanada5, Hideki Makishima1, Satoru Miyano3, Yukio Homma2, Seishi Ogawa1
  • Organizer: 2017 AACR Annual Meeting
  • Int'l Joint Research
• [Presentation] Comprehensive Genetic Analysis of Myxofibrosarcoma and Comparison with Other Soft Tissue Sarcomas (2017)
  • Author(s): Yasuhide Takeuchi, Annegret Kunitz, Hiromichi Suzuki, Kenichi Yoshida, Yuichi Shiraishi, Teppei Shimamura, Kenichi Chiba, Hiroko Tanaka, Nobuyuki Kakiuchi, Yusuke Shiozawa, Akira Yokoyama, Tetsuichi Yoshizato, Kosuke Aoki, Yoichi Fujii, Hideki Makishima, Hironori Haga, Satoru Miyano, Frederik Damm, Seishi Ogawa.
  • Organizer: 2017 AACR Annual Meeting
  • Int'l Joint Research
• [Presentation] The genetic aberrations in carcinogenic sequence of colitis-associated cancer (2017)
  • Author(s): Nobuyuki Kakiuchi,.et al.
  • Organizer: 2017 AACR Annual Meeting
  • Int'l Joint Research
• [Presentation] がんの免疫回避に関わる新たなメカニズムについて (2017)
  • Author(s): 小川 誠司
  • Organizer: 第54回日本臨床分子医学会学術集会
  • Invited
• [Presentation] 腎盂尿管癌における分子病態の解明とその臨床応用の可能性 (2017)
  • Author(s): Yoichi Fujii1,2, Yusuke Sato1, Hiromichi Suzuki2, Yusuke Shiozawa3, Tetsuichi Yoshizato2, Kenichi Yoshida2, Yuichi Shiraishi4, Tohru Nakagawa1, Haruki Kume1, Hiroaki Nishimatsu5, Toshikazu Okaneya6, Masashi Sanada7, Hideki Makishima2, Satoru Miyano4, Seishi Ogawa2, Yukio Homma1
  • Organizer: 日本泌尿器科学会総会
• [Presentation] Experimental pathology: Gene expression and gene mutation 3 (2017)
  • Author(s): 牧島秀樹
  • Organizer: The 106th Annual Meeting of the Japanese Society of Pathology
• [Presentation] The Aberrant Spliceosome Machinery (2017)
  • Author(s): Seishi Ogawa
  • Organizer: THE 14 th International SYMPOSIUM on MYELODYSPLASTIC SINDROMES
  • Int'l Joint Research / Invited
• [Presentation] Distinct Genomic Landscape of Upper Urinary Tract Urothelial Carcinoma (2017)
  • Author(s): Yoichi Fujii1, Yusuke Sato2, Hiromichi Suzuki1, Tetsuichi Yoshizato1, Yusuke Shiozawa1, Kenichi Yoshida1, Yuichi Shiraishi3, Tohru Nakagawa2, Haruki Kume2, Hiroaki Nishimatsu4, Toshikazu Okaneya5, Masashi Sanada6, Hideki Makishima1, Satoru Miyano3, , Seishi Ogawa, Yukio Homma
  • Organizer: American Urology Association
  • Int'l Joint Research
• [Presentation] Clonal hematopoiesis in aplastic anemia.-CLONAL DYNAMICS ESCAPING FROM AUTOIMMUNITY- (2017)
  • Author(s): Hideki Makishima
  • Organizer: Korean Society of Hematology
  • Int'l Joint Research / Invited
• [Presentation] 悪性腫瘍の遺伝学 (2017)
  • Author(s): 小川 誠司
  • Organizer: 芝蘭会学術講演会
  • Invited
• [Presentation] がんとゲノムの異常について (2017)
  • Author(s): 小川 誠司
  • Organizer: 第45回神戸ラボ全体研究会議
  • Invited
• [Presentation] A novel genetic and morphologic phenotype of ARID2-mediated myelodysplastic syndromes. (2017)
  • Author(s): Hitoshi Sakai ,.et al.
  • Organizer: 22nd Congress of European Hematology Association
  • Int'l Joint Research
• [Presentation] Transcriptome Sequencing Reveals Distinct Subtypes of Myelodysplasia with Prognostic Significance. (2017)
  • Author(s): Yusuke Shiozawa,.et al.
  • Organizer: 22nd Congress of European Hematology Association
  • Int'l Joint Research
• [Presentation] MOLECULAR MARKERS PREDICTING RESPONSE TO AZACITIDINE TREATMENT FOR MYELODYSPLASTIC SYNDROMES. (2017)
  • Author(s): Yasuhito Nannya,.et al.
  • Organizer: 22nd Congress of European Hematology Association
  • Int'l Joint Research
• [Presentation] GENETIC LANDSCAPE OF ACUTE ERYTHROID LEUKEMIA (2017)
  • Author(s): Hideki Makishima
  • Organizer: Hematology Meeting, University of Freiburg
  • Int'l Joint Research
• [Presentation] MDSにおける遺伝子変異と臨床像・予後について (2017)
  • Author(s): 小川 誠司
  • Organizer: 第7回日本骨髄不全症研究会学術集会
  • Invited
• [Presentation] 骨髄異形成症候群の分子病態 ー遺伝子変異の経時的な獲得ー (2017)
  • Author(s): 牧島秀樹
  • Organizer: 第15回 日本臨床腫瘍学会学術集会
  • Invited
• [Presentation] A novel mechanism of cancer immune evasion via the disruption of PD-L1 3’-UTR (2017)
  • Author(s): Seishi Ogawa
  • Organizer: Cold Spring Harbor Conferences Asia on Precision Cancer Biology & Medicine
  • Int'l Joint Research / Invited
• [Presentation] MDSの分子プロファイリング (2017)
  • Author(s): 小川 誠司
  • Organizer: 第24回岐阜血液疾患研究会
  • Invited
• [Presentation] A novel mechanism of cancer immune evasion via the disruption of PD-L1 3’-UTR (2017)
  • Author(s): Seishi Ogawa
  • Organizer: The Sixteenth Annual KICancer Retreat
  • Int'l Joint Research / Invited
• [Presentation] Frequent genetic aberrations involving programmed death ligands in virus-related lymphomas (2017)
  • Author(s): Keisuke Kataoka1,2, Seishi Ogawa1 (1Dept. Pathol. Tum. Biol., Grad. Sch. Med., Kyoto Univ., 2Div. Mol. Oncol., Natl. Cancer Cent. Res. Inst.)
  • Organizer: The 76th Annual Meeting of the Japanese Cancer Association
• [Presentation] Genome-wide analysis of DNA methylation and genetic alteration in pediatric T-cell acute lymphoblastic leukemia (TALL) (2017)
  • Author(s): Shunsuke Kimura,.et al.
  • Organizer: The 76th Annual Meeting of the Japanese Cancer Association
• [Presentation] A Novel Genetic Mechanism of Evading Anti-tumor Immunity In Multiple Human Cancers (2017)
  • Author(s): Seishi Ogawa
  • Organizer: The 76th Annual Meeting of the Japanese Cancer Association
• [Presentation] A novel mechanism of antitumor immunity in multiple human cancers (2017)
  • Author(s): Seishi Ogawa
  • Organizer: The 76th Annual Meeting of the Japanese Cancer Association
• [Presentation] A Novel Prediction Model Integrating Genomic and Clinical Features in Pediatric B-Cell Acute Lymphoblastic Leukemia (2017)
  • Author(s): Hiroo Ueno,.et al.
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] The carcinogenic sequence in colitis-associated cancer / 潰瘍性大腸炎関連大腸癌の発癌機序 (2017)
  • Author(s): 垣内 伸之、吉田 健一、塩澤 裕介、白石 友一、桜井 孝規、坂井 義治、内野 基、廣田 誠一、池内 浩基、宮野 悟、丸澤 宏之、妹尾 浩、小川 誠司
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Aplastic anemia and clonal evolution: risk factors (2017)
  • Author(s): Seishi Ogawa
  • Organizer: International Meeting on Childhood MDS and SAA
  • Int'l Joint Research / Invited
• [Presentation] Genomic Landscape of Upper Urinary Tract Urothelial Carcinoma (2017)
  • Author(s): Yoichi Fujii1,2, Yusuke Sato2, Hiromichi Suzuki1, Kenichi Yoshida1, Yuichi Shiraishi3, Tohru Nakagawa2, Haruki Kume2, Hiroaki Nishimatsu4, Toshikazu Okaneya5, Hideki Makishima1, Satoru Miyano3, Yukio Homma2, Seishi Ogawa
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Clonal evolution of atypical proliferative lesions into breast cancers/ 異型増殖性病変から乳癌へのクローン進化 (2017)
  • Author(s): Tomomi Nishimura, Kenichi Yoshida, Yukiko Kawata, Yusuke Shiozawa, Tatsuki R. Kataoka, Takaki Sakurai, Yuichi Shiraishi, Kenichi Chiba, Hironori Haga, Satoru Miyano, Masakazu Toi, Seishi Ogawa
  • Organizer: 第76回 日本癌学会学術総会
• [Presentation] Hereditary predisposition in sporadic and familial breast cancers / 散発性及び家族性乳癌における遺伝性素因 (2017)
  • Author(s): Yukiko Kawata, Kenichi Yoshida, Nobuko Kawaguchi-Sakita, Tomomi Nishimura, Yusuke Shiozawa, Hanako Shimizu, Eiji Suzuki, Yuichi Shiraishi, Kenichi Chiba, Ai Okada, Hiroko Tanaka, Satoru Miyano, Masakazu Toi and Seishi Ogawa
  • Organizer: The 76th Annual Meeting of Japanese Cancer Association
• [Presentation] Development of a method for high-throughput single-cell RNA sequencing with mutation information/多数の単一細胞における変異情報と発現プロファイルの同時測定手法の開発 (2017)
  • Author(s): Ryosaku Inagaki, Masahiro M Nakagawa, Yasuhito Nannya, Keisuke Kataoka, Tetsuichi Yoshizato, Hideki Makishima, Kenichi Yoshida, Seishi Ogawa
  • Organizer: The 76th Annual Meeting of Japanese Cancer Association
• [Presentation] 慢性的なアルコール・タバコの暴露が関与する食道発癌メカニズム (2017)
  • Author(s): 横山 顕礼, 垣内 伸之 , 鈴木 啓道, 吉里 哲一, 青木 恒一, 竹内 康英, 天沼 裕介, 西川 佳孝, 大橋 真也, 青山 育雄, 堀松 高博, 宮本 心一, 角田 茂, 南口 早智子, 武藤 学, 小川 誠司
  • Organizer: Japan digestive disease week 2017
• [Presentation] Novel mechanism of post-transcriptional regulation of PD-L1 expression by 3’-UTR binding proteins (2017)
  • Author(s): Yasunori Kogure, Keisuke Kataoka, Shungo Adachi, Yosaku Watatani, Ayana Kon, Kenichi Yoshida, Masahiro Nakagawa, Tomohisa Hatta, Tohru Natsume, Seishi Ogawa,
  • Organizer: 第79回日本血液学会学術集会
• [Presentation] A Novel Prediction Model Integrating Genomic and Clinical Features in Pediatric B-Cell Acute Lymphoblastic Leukemia (2017)
  • Author(s): Hiroo Ueno,.et al.
  • Organizer: 第79回日本血液学会学術集会
• [Presentation] Cohesin subunit Stag2 regulates Hematopoietic Differentiation and Self-Renewal (2017)
  • Author(s): Yotaro Ochi, Ayana Kon, Kenichi Yoshida, Keisuke Kataoka, Masahiro Marshall Nakagawa, Manabu Nakayama, Haruhiko Koseki, Akifumi Takaori-Kondo, and Seishi Ogawa
  • Organizer: 第79回日本血液学会学術総会
• [Presentation] A novel mechanism of cancer immune evasion vis 3'-UTR disruption of PD-L1 (2017)
  • Author(s): Seishi Ogawa
  • Organizer: the EMBL Cancer Genomics Conference 2017
  • Int'l Joint Research / Invited
• [Presentation] Clinical Effect of Genetic Alterations in Pediatric Patients with B-Progenitor Acute Lymphoblastic Leukemia (2017)
  • Author(s): Hiroo Ueno,.et al.
  • Organizer: The 59th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] IDH1/2-Mutated Acute Myeloid Leukemia Has Impaired DNA Damage Response and Is Sensitive to Monotherapy with the PARP Inhibitior Olaparib. (2017)
  • Author(s): Remco J Molenaar, Tomas Radivoyevitch, Yasunobu Nagata,Bartlomiej P. Przychodzen, Hideki Makishima, Hetty E. Carraway, Sudipto Mukherjee, Mikkael A. Sekeres, Cornelis van Noorden, and Jaroslaw P. Maciejewski
  • Organizer: The 59th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Novel Mechanism of Post-Transcriptional Regulation of PD-L1 Expression By 3’-UTR Binding Proteins (2017)
  • Author(s): Yasunori Kogure, Keisuke Kataoka, Shungo Adachi, Yosaku Watatani, Ayana Kon, Kenichi Yoshida, Masahiro Nakagawa, Tomohisa Hatta, Tohru Natsume and Seishi Ogawa
  • Organizer: The 59th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] 上部尿路上皮癌の網羅的ゲノム解析 (2017)
  • Author(s): Yoichi Fujii1, Yusuke Sato2, Hiromichi Suzuki1, Tetsuichi Yoshizato1, Yusuke Shiozawa1, Kenichi Yoshida1, Yuichi Shiraishi3, Tohru Nakagawa2, Hiroaki Nishimatsu4, Toshikazu Okaneya5, Masashi Sanada6, Hideki Makishima1, Satoru Miyano3, , Seishi Ogawa1 , Haruki Kume
  • Organizer: 泌尿器科分子・細胞研究会
• [Presentation] Integrated molecular analysis of upper urinary tract urothelial carcinoma" (2017)
  • Author(s): Yoichi Fujii1, Yusuke Sato2, Hiromichi Suzuki1, Tetsuichi Yoshizato1, Yusuke Shiozawa1, Kenichi Yoshida1, Yuichi Shiraishi3, Tohru Nakagawa2, Hiroaki Nishimatsu4, Toshikazu Okaneya5, Masashi Sanada6, Hideki Makishima1, Satoru Miyano3, , Seishi Ogawa1 , Haruki Kume
  • Organizer: European Urology Association
  • Int'l Joint Research
• [Presentation] Differential role of mutations in clonal evolution in of esophageal squamous cell mucosa in high-risk individuals for cancer (2017)
  • Author(s): Akira Yokoyama,.et al.
  • Organizer: American Association for Cancer Research 2017
  • Int'l Joint Research