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

2018 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): 牧島 秀樹 京都大学, 医学研究科, 准教授 (40402127) ; 南谷 泰仁 京都大学, 医学研究科, 特定准教授 (60451811) ; 佐藤 悠佑 東京大学, 医学部附属病院, 講師 (20372378)
• Project Period (FY): 2015-06-29 – 2020-03-31
• Keywords: RNAシーケンス / 総合生物 / 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。興味深いことに、前がん組織で認められた変異とがん組織で認められた変異のスペクトラムは大きく異なっていた。
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: 泌尿器系腫瘍(腎盂尿管癌)の全ゲノムシーケンスの解析により、MLL関連遺伝子において新規な変異が本病型に特異的かつ極めて高頻度に生じていることが明らかとなった。また、腎がんおよび膀胱がんとの遺伝子異常のプロファイルの違いに関しても新たな知見が得られた。
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が新たに5個同定された。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8%もの症例において認められ、MDSの発症には胚細胞変異が予想以上に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および、その他の大腸がんに関して、特徴的な遺伝子変異プロフアイルを有することを明らかにした。これらのうち予後と関連する因子を抽出し、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。食道がんに関しては論文化された（Yokoyama et al., Nature 2019）
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。全ゲノム解析により、それまで明らかとならなかった複雑な染色体コピー数異常および構造異常の合併が認められ、同部位から白血病の新たな治療標的遺伝子が発見され、論文化の予定である。
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。POLE変異陰性例に関しても、新たなドライバー遺伝子を検索中である。
以上より、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：大腸がん、すい臓がん、乳がん、泌尿器系腫瘍(腎盂尿管癌)について、前がん病変、健常組織を含めた組織から微小サンプリングを複数個所において行い、全エクソンシーケンスを行うことにより、がんの初期発生の過程を解明する。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500例、また成人T細胞白血病、尿路上皮がん、軟部肉腫についても、追加解析を行う。複雑な構造異常についてさらに詳細な解析を行う。
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、すい臓がんについて、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において、アレルドロップアウトの除去のプロトコールを確立し、今後の解析の精度が上昇した。
e)胚細胞系列の変異に関する解析：症例数をさらに追加して発症リスクをより詳細に推定する予定である。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、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、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引き続き試みる。

Research Products

• [Journal Article] Novel neuroblastoma amplified sequence (NBAS) mutations in a Japanese boy with fever-triggered recurrent acute liver failure. (2019)
  • Author(s): Ono S, Matsuda J, Watanabe E, Akaike H, Teranishi H, Miyata I, Otomo T, Sadahira Y, Mizuochi T, Kusano H, Kage M, Ueno H, Yoshida K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Hayashi Y, Kanegane H, Ouchi K.
  • Journal Title: Hum Genome Var Volume: 6:2. Pages: -
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  • Peer Reviewed / Open Access
• [Journal Article] Modification of cellular and humoral immunity by somatically reverted T cells in X-linked lymphoproliferative syndrome type 1. (2019)
  • Author(s): Hoshino A, Yang X, Tanita K, Yoshida K, Ono T, Nishida N, Okuno Y, Kanzaki T, Goi K, Fujino H, Ohshima K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Kojima S, Morio T, Kanegane H.
  • Journal Title: J Allergy Clin Immunol. Volume: 143(1) Pages: 421-424
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  • Peer Reviewed / Open Access
• [Journal Article] [Successful treatment of pure red cell aplasia with cyclosporin in a patient with T-cell large granular lymphocytic leukemia harboring the STAT3 D661V mutation] (2019)
  • Author(s): Adachi M, Yoshida K, Shiraishi Y, Chiba K, Miyano S, Ogawa S.
  • Journal Title: Rinsho Ketsueki. Volume: 60 Pages: 39-45.
  • DOI: 10.11406/rinketsu.60.39.
  • Peer Reviewed
• [Journal Article] Pathogenic mutations identified by a multimodality approach in 117 Japanese Fanconi anemia patients. (2019)
  • Author(s): Mori M, Hira A, Yoshida K, Muramatsu H, Okuno Y, Shiraishi Y, Anmae M, Yasuda J, Tadaka S, Kinoshita K, Osumi T, Noguchi Y, Adachi S, Kobayashi R, Kawabata H, Imai K, Morio T, Tamura K, Takaori-Kondo A, Yamamoto M, Miyano S, Kojima S, Ito E, Ogawa S, Matsuo K, Yabe H, Yabe M, Takata M.
  • Journal Title: Haematologica. Volume: - Pages: -
  • DOI: 10.3324/haematol.2018.207241.
  • Peer Reviewed
• [Journal Article] NOTCH1 pathway activating mutations and clonal evolution in pediatric T-cell acute lymphoblastic leukemia. (2019)
  • Author(s): Kimura S, Seki M, Yoshida K, Shiraishi Y, Akiyama M, Koh K, Imamura T, Manabe A, Hayashi Y, Kobayashi M, Oka A, Miyano S, Ogawa S, Takita J.
  • Journal Title: Cancer Sci. Volume: 110 Pages: 784-794
  • DOI: 10.1111/cas.13859
  • Open Access
• [Journal Article] Duplication of ALK F1245 missense mutation due to acquired uniparental disomy associated with aggressive progression in a patient with relapsed neuroblastoma. (2019)
  • Author(s): Kimura S, Hasegawa D, Yoshimoto Y, Seki M, Daida A, Sekiguchi M, Hirabayashi S, Hosoya Y, Kobayashi M, Miyano S, Ogawa S, Takita J, Manabe A.
  • Journal Title: Oncol Lett. Volume: 17 Pages: 3323-3329
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  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive analysis of genetic aberrations linked to tumorigenesis in regenerative nodules of liver cirrhosis. (2019)
  • Author(s): Kim SK, Takeda H, Takai A, Matsumoto T, Kakiuchi N, Yokoyama A, Yoshida K, Kaido T, Uemoto S, Minamiguchi S, Haga H, Shiraishi Y, Miyano S, Seno H, Ogawa S, Marusawa H.
  • Journal Title: J Gastroenterol. Volume: - Pages: -
  • DOI: 10.1007/s00535-019-01555-z.
  • Peer Reviewed / Open Access
• [Journal Article] Genetic and transcriptional landscape of plasma cells in POEMS syndrome. (2019)
  • Author(s): Nagao Y,Ogawa S., et al.
  • Journal Title: Leukemia. Volume: - Pages: -
  • DOI: 10.1038/s41375-018-0348-x.
  • Peer Reviewed / Open Access
• [Journal Article] Defective Epstein-Barr virus in chronic active infection and haematological malignancy. (2019)
  • Author(s): Okuno Y, Ogawa S., et al.
  • Journal Title: Nat Microbiol. Volume: 4(3) Pages: 544
  • DOI: 10.1038/s41564-019-0387-8.
  • Peer Reviewed / Open Access
• [Journal Article] Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas. (2019)
  • Author(s): Kataoka K, Ogawa S., et al.
  • Journal Title: Leukemia Volume: - Pages: -
  • DOI: 10.1038/s41375-019-0380-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Paraneoplastic hypereosinophilic syndrome associated with IL3-IgH positive acute lymphoblastic leukemia (2019)
  • Author(s): Kobayashi K, Mizuta S, Yamane N, Ueno H, Yoshida K, Kato I, Umeda K, Hiramatsu H, Suehiro M, Maihara T, Usami I, Shiraishi Y, Chiba K, Miyano S, Adachi S, Ogawa S, Kiyokawa N, Heike T
  • Journal Title: Pediatr Blood Cancer Volume: 66 Pages: e27499
  • Peer Reviewed
• [Journal Article] Frequent germline mutations of HAVCR2 in sporadic subcutaneous panniculitis-like T-cell lymphoma. (2019)
  • Author(s): Polprasert C, Takeuchi Y, Kakiuchi N, Yoshida K, Assanasen T, Sitthi W, Bunworasate U, Pirunsarn A, Wudhikarn K, Lawasut P, Uaprasert N, Kongkiatkamon S, Moonla C, Sanada M, Akita N, Takeda J, Fujii Y, Suzuki H, Nannya Y, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Rojnuckarin P, Ogawa S, Makishima H
  • Journal Title: Blood Adv. Volume: 3 Pages: 588-595
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  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Age-related remodelling of oesophageal epithelia by mutated cancer drivers. (2019)
  • Author(s): Yokoyama A, Ogawa S., et al.
  • Journal Title: Nature Volume: 565 Pages: 312-317
  • DOI: 10.1038/s41586-018-0811-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Whole-exome analysis to detect congenital hemolytic anemia mimicking congenital dyserythropoietic anemia. (2018)
  • Author(s): Hamada M, Doisaki S, Okuno Y, Muramatsu H, Hama A, Kawashima N, Narita A, Nishio N, Yoshida K, Kanno H, Manabe A, Taga T, Takahashi Y, Miyano S, Ogawa S, Kojima S.
  • Journal Title: Int J Hematol. Volume: 108 Pages: 306-311
  • DOI: 10.1007/s12185-018-2482-7.
  • Peer Reviewed
• [Journal Article] Gain-of-function IKBKB mutation causes human combined immune deficiency. (2018)
  • Author(s): Cardinez C, Miraghazadeh B, Tanita K, da Silva E, Hoshino A, Okada S, Chand R, Asano T, Tsumura M, Yoshida K, Ohnishi H, Kato Z, Yamazaki M, Okuno Y, Miyano S, Kojima S, Ogawa S, Andrews TD, Field MA, Burgio G, Morio T, Vinuesa CG, Kanegane H, Cook MC.
  • Journal Title: J Exp Med. Volume: 215 Pages: 2715-2724.
  • DOI: 10.1084/jem.20180639.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. (2018)
  • Author(s): Aoki K, Nakamura H, Suzuki H, Matsuo K, Kataoka K, Shimamura T, Motomura K, Ohka F, Shiina S, Yamamoto T, Nagata Y, Yoshizato T, Mizoguchi M, Abe T, Momii Y, Muragaki Y, Watanabe R, Ito I, Sanada M, Yajima H, Morita N, Takeuchi I, Miyano S, Wakabayashi T, Ogawa S, Natsume A.
  • Journal Title: Neuro Oncol. Volume: 20 Pages: 66-67
  • DOI: 10.1093/neuonc/nox132.
  • Peer Reviewed / Open Access
• [Journal Article] Distinct gene alterations with a high percentage of myeloperoxidase-positive leukemic blasts in de novo acute myeloid leukemia. (2018)
  • Author(s): Kamijo R, Itonaga H, Kihara R, Nagata Y, Hata T, Asou N, Ohtake S, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Naoe T, Kiyoi H, Miyazaki Y.
  • Journal Title: Leuk Res. Volume: 65 Pages: 34-41.
  • DOI: 10.1016/j.leukres.2017.12.006
  • Peer Reviewed / Open Access
• [Journal Article] Intensive Treat-to-Target Statin Therapy in High-Risk Japanese Patients With Hypercholesterolemia and Diabetic Retinopathy: Report of a Randomized Study. (2018)
  • Author(s): Itoh H, Ogawa S., et al.
  • Journal Title: Diabetes Care. Volume: 41 Pages: 1275-1284.
  • DOI: 10.2337/dc17-2224.
  • Peer Reviewed / Open Access
• [Journal Article] Dysregulation of Epstein-Barr Virus Infection in Hypomorphic ZAP70 Mutation. (2018)
  • Author(s): Hoshino A, Takashima T, Yoshida K, Morimoto A, Kawahara Y, Yeh TW, Okano T, Yamashita M, Mitsuiki N, Imai K, Sakatani T, Nakazawa A, Okuno Y, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Kojima S, Morio T, Kanegane H.
  • Journal Title: J Infect Dis. Volume: 218 Pages: 825-834.
  • DOI: 10.1093/infdis/jiy231.
  • Peer Reviewed / Open Access
• [Journal Article] RUNX1 mutations in pediatric acute myeloid leukemia are associated with distinct genetic features and an inferior prognosis. (2018)
  • Author(s): Yamato G, Shiba N, Yoshida K, Hara Y, Shiraishi Y, Ohki K, Okubo J, Park MJ, Sotomatsu M, Arakawa H, Kiyokawa N, Tomizawa D, Adachi S, Taga T, Horibe K, Miyano S, Ogawa S, Hayashi Y.
  • Journal Title: Blood. Volume: 131 Pages: 2266-2270.
  • DOI: 10.1182/blood-2017-11-814442.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] De Novo Mutations Activating Germline TP53 in an Inherited Bone-Marrow-Failure Syndrome. (2018)
  • Author(s): Toki T, Ogawa S., et al.
  • Journal Title: Am J Hum Genet. Volume: 103 Pages: 440-447
  • DOI: 10.1016/j.ajhg.2018.07.020.
  • Peer Reviewed / Open Access
• [Journal Article] Genetic heterogeneity of uncharacterized childhood autoimmune diseases with lymphoproliferation. (2018)
  • Author(s): Takagi M, Hoshino A, Yoshida K, Ueno H, Imai K, Piao J, Kanegane H, Yamashita M, Okano T, Muramatsu H, Okuno Y, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Hayashi Y, Kojima S, Morio T.
  • Journal Title: Pediatr Blood Cancer. Volume: 65 Pages: -
  • DOI: 10.1002/pbc.26831.
  • Peer Reviewed / Open Access
• [Journal Article] A comprehensive characterization of cis-acting splicing-associated variants in human cancer. (2018)
  • Author(s): Shiraishi Y, Kataoka K, Chiba K, Okada A, Kogure Y, Tanaka H, Ogawa S, Miyano S.
  • Journal Title: Genome Res. Volume: 28 Pages: 1111-1125.
  • DOI: 10.1101/gr.231951.117.
  • Peer Reviewed
• [Journal Article] A novel genetic and morphologic phenotype of ARID2-mediated myelodysplasia. (2018)
  • Author(s): Sakai H, Hosono N, Nakazawa H, Przychodzen B, Polprasert C, Carraway HE, Sekeres MA, Radivoyevitch T, Yoshida K, Sanada M, Yoshizato T, Kataoka K, Nakagawa MM, Ueno H, Nannya Y, Kon A, Shiozawa Y, Takeda J, Shiraishi Y, Chiba K, Miyano S, Singh J, Padgett RA, Ogawa S, Maciejewski JP, Makishima H.
  • Journal Title: Leukemia. Volume: 32 Pages: 839-843
  • DOI: 10.1038/leu.2017.319.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integrated molecular profiling of juvenile myelomonocytic leukemia. (2018)
  • Author(s): Murakami N, Okuno Y, Yoshida K, Shiraishi Y, Nagae G, Suzuki K, Narita A, Sakaguchi H, Kawashima N, Wang X, Xu Y, Chiba K, Tanaka H, Hama A, Sanada M, Ito M, Hirayama M, Watanabe A, Ueno T, Kojima S, Aburatani H, Mano H, Miyano S, Ogawa S, Takahashi Y, Muramatsu H.
  • Journal Title: Blood. Volume: 131 Pages: 1576-1586
  • DOI: 10.1182/blood-2017-07-798157
  • Peer Reviewed / Open Access
• [Journal Article] Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia. (2018)
  • Author(s): Matsuo H, Ogawa S., et al.
  • Journal Title: Blood Adv. Volume: 2 Pages: 2879-2889.
  • DOI: 10.1182/bloodadvances.2018019398.
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma. (2018)
  • Author(s): Kataoka K, Ogawa S., et al.
  • Journal Title: Blood. Volume: 131 Pages: 215-225.
  • DOI: 10.1182/blood-2017-01-761874
  • Peer Reviewed / Open Access
• [Journal Article] Hidden FLT3-D835Y clone in FLT3-ITD-positive acute myeloid leukemia that evolved into very late relapse with T-lymphoblastic leukemia. (2018)
  • Author(s): Katagiri S, Umezu T, Azuma K, Asano M, Akahane D, Makishima H, Yoshida K, Watatani Y, Chiba K, Miyano S, Ogawa S, Ohyashiki JH, Ohyashiki K.
  • Journal Title: Leuk Lymphoma. Volume: 59 Pages: 1490-1493.
  • DOI: 10.1080/10428194.2017.
  • Peer Reviewed
• [Journal Article] Clonally related diffuse large B-cell lymphoma and interdigitating dendritic cell sarcoma sharing MYC translocation. (2018)
  • Author(s): Ochi Y, Hiramoto N, Yoshizato T, Ono Y, Takeda J, Shiozawa Y, Yoshida K, Kakiuchi N, Shiraishi Y, Tanaka H, Chiba K, Kazuma Y, Tabata S, Yonetani N, Uehara K, Yamashita D, Imai Y, Nagafuji K, Yamakawa M, Miyano S, Takaori-Kondo A, Ogawa S, Ishikawa T.
  • Journal Title: Haematologica Volume: 103 Pages: e553-e556
  • DOI: 10.3324/haematol.2018.193490.
  • Peer Reviewed / Open Access
• [Journal Article] Hidden FLT3-D835Y clone in FLT3-ITD-positive acute myeloid leukemia that evolved into very late relapse with T-lymphoblastic leukemia. (2018)
  • Author(s): Katagiri S, Umezu T, Azuma K, Asano M, Akahane D, Makishima H, Yoshida K, Watatani Y, Chiba K, Miyano S, Ogawa S, Ohyashiki JH, Ohyashiki K
  • Journal Title: Leuk Lymphoma Volume: 59 Pages: 1490-1493
  • DOI: 10.1080/10428194.2017.1382696
  • Peer Reviewed / Open Access
• [Journal Article] A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer. (2018)
  • Author(s): Saito T, Ogawa S., et al.
  • Journal Title: Nat Commun. Volume: 9 Pages: 2884
  • DOI: 10.1038/s41467-018-05226-0
  • Peer Reviewed / Open Access
• [Journal Article] Aberrant splicing and defective mRNA production induced by somatic spliceosome mutations in myelodysplasia. (2018)
  • Author(s): Shiozawa Y, Malcovati L, Gall A, Sato-Otsubo A, Kataoka K, Sato Y, Watatani Y, Suzuki H, Yoshizato T, Yoshida K, Sanada M, Makishima H, Shiraishi Y, Chiba K, Hellstrom-Lindberg E, Miyano S, Ogawa S, Cazzola M
  • Journal Title: Nat. Commun. Volume: 9 Pages: 3649
  • DOI: 10.1038/s41467-018-06063-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Early detection and evolution of preleukemic clones in therapy-related myeloid neoplasms following autologous SCT (2018)
  • Author(s): Berger G,Ogawa S., et al.
  • Journal Title: Blood Volume: 131 Pages: 1846-1857
  • DOI: 10.1182/blood-2017-09-805879
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular pathogenesis of disease progression in MLL-rearranged AML. (2018)
  • Author(s): 10.1038/s41375-018-0253-3
  • Journal Title: Leukemia Volume: 33 Pages: 612-614
  • DOI: 10.1038/s41375-018-0253-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia. (2018)
  • Author(s): "Matsuo H, Ogawa S., et al.
  • Journal Title: Blood Adv. Volume: 13 Pages: 2879-2889
  • DOI: 10.1182/bloodadvances.2018019398
  • Peer Reviewed / Open Access
• [Presentation] Comprehensive analysis of genetic alterations and intratumor heterogeneity in myxofibrosarcoma (2018)
  • 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: American Association for Cancer Research Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] Integrated molecular analysis of Upper Urinary Tract Urothelial Carcinoma (2018)
  • Author(s): Yoichi Fujii, Yusuke Sato, Hiromichi Suzuki, Tetsuichi Yoshizato, Kenichi Yoshida, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Tohru Nakagawa, Hiroaki Nishimatsu, Yoshikazu Hirano, Masashi Sanada, Hideki Makishima, Satoru Miyano, Yukio Homma, Haruki Kume, Seishi Ogawa
  • Organizer: American Association of Cancer Research (AACR)
  • Int'l Joint Research
• [Presentation] Clonal evolution of atypical proliferative lesions into breast cancers (2018)
  • Author(s): Tomomi Nishimura, Kenichi Yoshida, Yukiko Kawata, Yasuhide Takeuchi, Nobuyuki Kakiuchi, Yusuke Shiozawa, Kosuke Aoki, Masahiro Hirata, Tatsuki R. Kataoka, Takaki Sakurai, Yuichi Shiraishi, Kenichi Chiba, Kengo Takeuchi, Hironori Haga, Satoru Miyano, Masakazu Toi, Seishi Ogawa
  • Organizer: AACR Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] Genetic Landscape and Clonal Expansion of Upper Urinary Tract Urothelial Carcinoma (2018)
  • Author(s): Yoichi Fujii, Yusuke Sato, Hiromichi Suzuki, Tetsuichi Yoshizato, Kenichi Yoshida, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Tohru Nakagawa, Hiroaki Nishimatsu, Yoshikazu Hirano, Masashi Sanada, Hideki Makishima, Satoru Miyano, Yukio Homma, Seishi Ogawa, Haruki Kume
  • Organizer: Japan Urology Association (JUA)
• [Presentation] 乳管上皮異型増殖性病変から乳癌へ至るクローン進化 (2018)
  • Author(s): 西村友美、吉田健一,_川田有希子,_竹内康英,_垣内伸之,_塩澤裕介,_青木恒介,_平田勝啓,_片岡竜貴,_桜_井孝規,_白石友一,_千葉健一,_竹内賢吾,_羽賀博典,_宮野悟,_戸井雅和,_小川誠司
  • Organizer: The 26th Annual Meeting of The Japanese Breast Cancer Society
• [Presentation] 成人T細胞白血病の分子基盤とがんの免疫回避に関わる新たなメカニズムについて/Molecular basis of adult T-cell leukemia/lymphoma, focusing on cancer immune evasion (2018)
  • Author(s): 小川誠司
  • Organizer: 第22回日本がん分子標的治療学会
  • Invited
• [Presentation] Comprehensive analysis of Upper Urinary Tract Urothelial Carcinoma (2018)
  • Author(s): Yoichi Fujii, Yusuke Sato, Hiromichi Suzuki, Tetsuichi Yoshizato, Kenichi Yoshida, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Tohru Nakagawa, Hiroaki Nishimatsu, Yoshikazu Hirano, Masashi Sanada, Hideki Makishima, Satoru Miyano, Yukio Homma, Seishi Ogawa, Haruki Kume
  • Organizer: American Urology Association (AUA)
  • Int'l Joint Research
• [Presentation] Clonal evolution in myelodysplastic syndrome (2018)
  • Author(s): Seishi Ogawa
  • Organizer: 6th TSH International Symposium
  • Int'l Joint Research / Invited
• [Presentation] Somatic and Germline Mutations in Myelodysplastic Syndromes. (2018)
  • Author(s): Hideki Makishima
  • Organizer: The 6th TSH International Symposium.
  • Invited
• [Presentation] MOLECULAR PATHOGENESIS OF DISEASE PROGRESSION IN MLLREARRANGED AML (2018)
  • Author(s): Shinichi Kotani , Seishi Ogawa., et al.
  • Organizer: 23rd Congress of European Hematology Association (EHA)
  • Int'l Joint Research
• [Presentation] Stag2 regulates hematopoietic differentiation and self-renewal (2018)
  • Author(s): Yotaro Ochi, Ayana Kon, Masahiro Marshall Nakagawa, Keisuke Kataoka, Kenichi Yoshida, Haruhiko Koseki, Manabu Nakayama, Akinori Yoda, Hideki Makishima, Akifumi Takaori-Kondo2, and Seishi Ogawa
  • Organizer: 23rd Congress of European Hematology Association (EHA)
  • Int'l Joint Research
• [Presentation] 3’‐UTR disruption of PD‐L1 in malignant lymphomas (2018)
  • Author(s): Seishi Ogawa
  • Organizer: Inaugural AACR International Meeting
  • Int'l Joint Research / Invited
• [Presentation] New targetes and biomarkers in hematological malignancies (2018)
  • Author(s): Seishi Ogawa
  • Organizer: 18th World Congress of Basic and Clinical Pharmacology
  • Int'l Joint Research / Invited
• [Presentation] Stag2 Regulates Hematopoietic Differentiation and Self-Renewal (2018)
  • Author(s): Seishi Ogawa
  • Organizer: The 9th JSH International Symposium
  • Int'l Joint Research / Invited
• [Presentation] PD-1/PD-L1-mediated immune evasion of virus-associated lymphomas (2018)
  • Author(s): Seishi Ogawa
  • Organizer: Hematology Research Unit Helsinki (HRUH) Visit August 20th
• [Presentation] Interim analysis of 300 whole genomes of myeloid malignancies (2018)
  • Author(s): Seishi Ogawa
  • Organizer: KAW Conference on Normal & Malignant Hematopoiesis
  • Int'l Joint Research / Invited
• [Presentation] Sequential acquisition of mutations in myelodysplastic syndromes (2018)
  • Author(s): Hideki Makishima
  • Organizer: 41st IRCMS Seminar
  • Invited
• [Presentation] Mechanisms of the clonal evolution of MDS as revealed by single-cell sequencing. (2018)
  • Author(s): Masahiro M Nakagawa, Ryosaku Inagaki, Yasuhito Nannya, Zhao Lanying, June Takeda, Akinori Yoda, Ayana Kon, Tetsuichi Yoshizato, Hideki Makishima, and Seishi Ogawa
  • Organizer: 77th Anulal Meeeting of the Japanese Cancer Association
  • Int'l Joint Research / Invited
• [Presentation] Prognostic impact of POLE mutation in Colorectal Cancer (2018)
  • Author(s): Yoshikage Inoue, Nobuyuki Kakiuchi, Kenichi Yoshida, Yusuke Shiozawa, Yuichi Shiraishi, Kenichi Chiba, Tetsuichi Yoshizato, Yasuhide Takeuchi, Satoshi Nagayama, Satoru Miyano, Yoshiharu Sakai, Seishi Ogawa
  • Organizer: 77th Anulal Meeeting of the Japanese Cancer Association
  • Int'l Joint Research / Invited
• [Presentation] Comprehensive analysis for genetic factors predictive of azacitidine treatment for MDS. (2018)
  • Author(s): Yasuhito Nannya, June Takeda, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Akifumi Takaori, Shigeru Chiba, Kazuma Ohyashiki, Yasushi Miyazaki, Tomoki Naoe, Satoru Miyano, Seishi Ogawa
  • Organizer: 77th Anulal Meeeting of the Japanese Cancer Association
  • Int'l Joint Research / Invited
• [Presentation] Age-related remodeling of apparently normal esophageal epithelia by common cancer drivers (2018)
  • Author(s): 横山顕礼、吉里哲一、垣内伸之、南谷泰仁、鈴木啓道、塩澤祐介、佐藤悠佑、竹内康英、牧島秀樹、角田茂、真田昌、宮野悟、武藤学、小川誠司
  • Organizer: 77th Anulal Meeeting of the Japanese Cancer Association
• [Presentation] 上部尿路上皮癌の網羅的ゲノム解析 (2018)
  • Author(s): Yoichi Fujii, Yusuke Sato, Hiromichi Suzuki, Tetsuichi Yoshizato, Kenichi Yoshida, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Tohru Nakagawa, Hiroaki Nishimatsu, Yoshikazu Hirano, Masashi Sanada, Hideki Makishima, Satoru Miyano, Yukio Homma, Haruki Kume, Seishi Ogawa
  • Organizer: 77th Anulal Meeeting of the Japanese Cancer Association
• [Presentation] Clonal evolution of non-malignant proliferative lesions into breast cancers (2018)
  • Author(s): Tomomi Nishimura, Kenichi Yoshida, Yasuhide Takeuchi, Nobuyuki Kakiuchi, Yusuke Shiozawa, Tatsuki R. Kataoka, Takaki Sakurai, Kengo Takeuchi, Hironori Haga, Satoru Miyano, Masakazu Toi, Seishi Ogawa
  • Organizer: The 77th Annual Meeting of the Japanese Cancer Association
• [Presentation] ビッグデータ解析 (2018)
  • Author(s): Seishi Ogawa
  • Organizer: The 77th Annual Meeting of the Japanese Cancer Association
  • Invited
• [Presentation] Genetic Analysis of Pancreatic Neuroendocrine Neoplasms Grade 3 / 膵神経内分泌癌の網羅的ゲノム解析 (2018)
  • Author(s): 垣内 伸之、平野 智紀、竹内 康英、塩澤 裕介、吉澤 明彦、白石 友一、宮野 悟、肱岡 範、谷田部 恭、妹尾 浩、児玉 裕三、小川 誠司
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] 高リスクMDSの新規治療について (2018)
  • Author(s): 南谷泰仁
  • Organizer: The 80th Annual Meeting of the Japanese Society of Hematology
  • Invited
• [Presentation] Comprehensive analysis for genetic factors predictive of azacitidine treatment for MDS. (2018)
  • Author(s): Yasuhito Nannya,Seishi Ogawa.,et al.
  • Organizer: The 80th Annual Meeting of the Japanese Society of Hematology
• [Presentation] 造血器腫瘍の治療におけるNGSパネルの利用 (2018)
  • Author(s): Seishi Ogawa
  • Organizer: The 80th Annual Meeting of the Japanese Society of Hematology
  • Invited
• [Presentation] Impact of genetic alterations in stem cell transplantation for myelodysplastic syndromes (2018)
  • Author(s): Tetsuichi Yoshizato
  • Organizer: The 80th Annual Meeting of the Japanese Society of Hematology
  • Int'l Joint Research
• [Presentation] 網羅的ゲノム解析による膵神経内分泌癌の分_病態の解明と治療薬選択への展望 (2018)
  • Author(s): 垣内 伸之、児玉 裕三、小川 誠司
  • Organizer: JDDW 2018 KOBE
• [Presentation] Sequential acquisition of genetic mutations (2018)
  • Author(s): Hideki Makishima
  • Organizer: Annual Colloquium
• [Presentation] Analysis of clonal evolution/heterogeneity of MDS by simultaneous detection of both mutation and gene expression by single cell sequencing (2018)
  • Author(s): Masahiro Marshall Nakagawa, Ryosaku Inagaki, Yasuhito Nannya, Lanying Zhao, Yutaka Kuroda, June Takeda, Xingxing Qi, Akinori Yoda, Ayana Kon, Hisashi Tsurumi, Hideki Makishima, Shuichi Matsuda and Seishi Ogawa
  • Organizer: 60th ASH Annual Meeting
  • Int'l Joint Research
• [Presentation] Genome-wide analysis of non-coding alterations in pan-myeloid cancers using whole genome sequencing. (2018)
  • Author(s): Yasuhito Nannya, Seishi Ogawa., et al.
  • Organizer: 60th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Novel and Significant Impact of Germline Variants Predisposed to Pathogenic Somatic Mutations and Loss of Heterozygosity (LOH) in Myelodysplastic Syndromes (MDS) and Clonal Hematopoiesis of Indeterminate Potential (CHIP) (2018)
  • Author(s): Hideki_Makishima,Seishi Ogawa., et al.
  • Organizer: 60th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Invariant Patterns of Clonal Succession Determines Specific Phenotypic and Clinical Features of Myelodysplastic Syndromes (MDS) (2018)
  • Author(s): Yasunobu_Nagata,Seishi Ogawa., et al.
  • Organizer: 60th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Genomic Analysis of Myelodysplastic Syndromes Among Nagasaki Atomic Bomb Survivors (2018)
  • Author(s): Masataka_Taguchi,Seishi Ogawa., et al.
  • Organizer: 61st American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Pan-Myeloid Leukemia Analysis: Machine Learning-Based Approach to Predict Phenotype and Clinical Outcomes Using Mutation Data (2018)
  • Author(s): Kiyomi_Moritaia,Seishi Ogawa., et al.
  • Organizer: 62nd American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Clonal evolution of non-malignant proliferative lesions into breast cancers (2018)
  • Author(s): Tomomi Nishimura, Kenichi Yoshida, Yukiko Kawata, Yasuhide Takeuchi, Nobuyuki Kakiuchi, Yusuke Shiozawa, Kosuke Aoki, Masahiro Hirata, Tatsuki R. Kataoka, Takaki Sakurai, Satoko Baba, Yuichi Shiraishi, Kenichi Chiba, Kengo Takeuchi, Hironori Haga, Satoru Miyano, Masakazu Toi, Seishi Ogawa
  • Organizer: San Antonio Breast Cancer Symposium 2018
  • Int'l Joint Research
• [Presentation] STAG2 mutations alter epigenic and transcriptional dynamics in myeloid neoplasms (2018)
  • Author(s): Ayana Kon
  • Organizer: Meeting of Leukemic and Hematopoietic Stem Cells in Tokyo
  • Invited
• [Presentation] 上部尿路上皮癌の網羅的ゲノム解析 (2018)
  • Author(s): Yoichi Fujii, Yusuke Sato, Hiromichi Suzuki, Tetsuichi Yoshizato, Kenichi Yoshida, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Tohru Nakagawa, Hiroaki Nishimatsu, Yoshikazu Hirano, Masashi Sanada, Hideki Makishima, Satoru Miyano, Yukio Homma, Seishi Ogawa, Haruki Kume
  • Organizer: 泌尿器科分子・細胞研究会
• [Presentation] On the Origin of Human Cancer (2018)
  • Author(s): Seishi Ogawa
  • Organizer: Institute for the Advanced Study of Human Biology (ASHBi)
• [Presentation] Integrated molecular analysis of Upper Urinary Tract Urothelial Carcinoma (2018)
  • Author(s): Yoichi Fujii, Yusuke Sato, Hiromichi Suzuki, Tetsuichi Yoshizato, Kenichi Yoshida, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Tohru Nakagawa, Hiroaki Nishimatsu, Yoshikazu Hirano, Masashi Sanada, Hideki Makishima, Satoru Miyano, Yukio Homma, Seishi Ogawa, Haruki Kume
  • Organizer: European Association of Urology(EAU)
  • Int'l Joint Research
• [Presentation] Myxofibrosarcoma is characterized by frequent abnormalities in TP53 and increased genetic instability (2018)
  • 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: American Association for Cancer Research Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] Clonal evolution of non-malignant proliferative lesions into breast cancers (2018)
  • Author(s): Tomomi Nishimura, Kenichi Yoshida, Yukiko Kawata, Yasuhide Takeuchi, Nobuyuki Kakiuchi, Yusuke Shiozawa, Kosuke Aoki, Masahiro Hirata, Tatsuki R. Kataoka, Takaki Sakurai, Satoko Baba, Yuichi Shiraishi, Kenichi Chiba, Kengo Takeuchi, Hironori Haga, Satoru Miyano, Masakazu Toi, Seishi Ogawa
  • Organizer: AACR Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] Mutational landscape of colorectal cancer with POLE gene mutation (2018)
  • Author(s): Yoshikage Inoue, Nobuyuki Kakiuchi, Kenichi Yoshida, Yusuke Shiozawa, Yuichi Shiraishi, Kenichi Chiba, Tetsuichi Yoshizato, Hiroko Tanaka, Ai Okada, Satoshi Nagayama, Satoru Miyano, Yoshiharu Sakai,Seishi Ogawa
  • Organizer: American Association of Cancer Research (AACR)
  • Int'l Joint Research
• [Presentation] Genetic analysis of metachronous pancreatic cancers (2018)
  • Author(s): T. Hirano, Y. Takeuchi, N. Kakiuchi, S. Minamiguchi, H. Haga, Y. Kodama, N. Uza, H. Seno, S. Uemoto, T. Masui, K. Yoshida , Y. Shiozawa , K. Chiba , T. Yoshizato , Y.Shiraishi , S. Miyano , S. Ogawa
  • Organizer: American Association of Cancer Research (AACR)
  • Int'l Joint Research
• [Remarks]
  • URL: https://www.med.kyoto-u.ac.jp/organization-staff/research/doctoral_course/r-006/
• [Remarks]
  • URL: http://plaza.umin.ac.jp/kyoto_tumorpatho/
• [Remarks]
  • URL: https://researchmap.jp/7000009356/