2016 Fiscal Year Annual Research Report
Comprehensive and spationtemporal genetic analyses of clonal evolution of metastatic and recurrent pediatric solid tumors
| Project/Area Number |
26293242
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| Research Institution | The University of Tokyo |
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Principal Investigator |
滝田 順子 東京大学, 医学部附属病院, 准教授 (00359621)
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| Co-Investigator(Kenkyū-buntansha) |
安戸 裕貴 東京大学, 医学部附属病院, 助教 (70422285)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 小児難治性腫瘍 / 神経芽腫 / ゲノムコピー数の異常 / クローン進化 / ALK / MYCN |
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| Outline of Annual Research Achievements |
難治性小児がんの代表である神経芽腫500例につき、がん関連遺伝子10個のターゲットシーケンスと高密度SNPアレイ解析を用いて、ゲノムプロファイリングを行った。その結果、神経芽腫は、ゲノム異常の特性により6つのサブグループに分類されることが判明した。これらのサブグループは臨床的特徴とよく相関し、さらに興味深いことに腫瘍の進化の過程を反映していることが明らかとなった。サブグループは以下の通りである。グループA (ALK異常を伴う群)、グループB (他の遺伝子変異を伴う群)、グループC (MYCN増幅を伴う群)、グループD (11q LOHを伴う群)、グループE (少なくとも1か所のゲノムコピー数の変化を伴う群)およびグループF (サイレント群)。グループAからDは予後不良であり、グループE、Fは予後良好であった。 サブグループAからEを通じて、最も共通するゲノム異常は、17qの増加であったことから、神経芽腫の発生過程において、17qの増加は最も早期に生じる異常であることが推測できた。また、次に高頻度なゲノム異常は2pの増加であったことから、これは17qの増加に引き続いて生じた異常であり、その後、1p LOHおよび11q LOHが排他的に独立したクローンに生じた可能性が考えられた。その後、1p LOHをもつクローンにALK変異とMYCN増幅がそれぞれ別々に生じ、異なるサブグループに分化していったものと推測された。グループEでは、hyperploidが高頻度であったことから、同時に染色体の異数分裂が生じた結果、腫瘍化したものと推測された。またグループFにおけるがん化のメカニズムには、生殖系列細胞の異常やエピゲノム異常の関与が考えられた。以上の結果より、大多数のコホートに対するゲノムのプロファイリングは、腫瘍の進化を推測する上でも有用であった。
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| Research Progress Status |
28年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
28年度が最終年度であるため、記入しない。
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| Causes of Carryover |
28年度が最終年度であるため、記入しない。
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| Expenditure Plan for Carryover Budget |
28年度が最終年度であるため、記入しない。
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[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.
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Journal Title
Pediatr Blood Cancer.
Volume: in press
Pages: -
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Partial monosomy of 10p and duplication of another chromosome in two patients.2017
Author(s)
Ohta S, Isojima T, Mizuno Y, Kato M, Mimaki M, Seki M, Sato Y, Ogawa S, Takita J, Kitanaka S, Oka A.
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Journal Title
Pediatr Int.
Volume: 59
Pages: 99-102
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] ZNF384-related fusion genes consist of a subgroup with a characteristic immunophenotype in childhood B-cell precursor acute lymphoblastic leukemia.2017
Author(s)
Hirabayashi S, Ohki K, Nakabayashi K, Ichikawa H, Momozawa Y, Okamura K, Yaguchi A, Terada K, Saito Y, Yoshimi A, Ogata-Kawata H, Sakamoto H, Kato M, Fujimura J, Hino M, Kinoshita A, Kakuda H, Kurosawa H, Kato K, Kajiwara R, Moriwaki K, Morimoto T, Nakamura K, Noguchi Y, Osumi T, Sakashita K, Takita J, et al.
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Journal Title
Haematologica.
Volume: 102
Pages: 118-129
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[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.
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Journal Title
Leukemia.
Volume: 31
Pages: 580-584
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults.2016
Author(s)
Yasuda T, Tsuzuki S, Kawazu M, Hayakawa F, Kojima S, Ueno T, Imoto N, Kohsaka S, Kunita A, Doi K, Sakura T, Yujiri T, Kondo E, Fujimaki K, Ueda Y, Aoyama Y, Ohtake S, Takita J, Sai E, Taniwaki M, Kurokawa M, Morishita S, Fukayama M, Kiyoi H, Miyazaki Y, Naoe T, Mano H.
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Journal Title
Nat Genet.
Volume: 48
Pages: 569-574
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Whole-exome sequencing reveals the spectrum of gene mutations and the clonal evolution patterns in paediatric acute myeloid leukaemia.2016
Author(s)
Shiba N, Yoshida K, Shiraishi Y, Okuno Y, Yamato G, Hara Y, Nagata Y, Chiba K, Tanaka H, Terui K, Kato M, Park MJ, Ohki K, Shimada A, Takita J, Tomizawa D, Kudo K, Arakawa H, Adachi S, Taga T, Tawa A, Ito E, Horibe K, Sanada M, Miyano S, Ogawa S, Hayashi Y.
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Journal Title
Br J Haematol.
Volume: 175
Pages: 476-489
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Adults with germline CBL mutation complicated with juvenile myelomonocytic leukemia at infancy.2016
Author(s)
Muraoka M, Okuma, C, Kanamitsu K, Ishida H, Kanazawa Y, Washino K, Seki M, Kato M, Takita J, Sato Y, Ogawa S, Tsukahara H, Oda M.
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Journal Title
J Hum Genet.
Volume: 61
Pages: 523-526
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] ALKR1275Q perturbs extracellular matrix, enhances cell invasion, and leads to the development of neuroblastoma in cooperation with MYCN.2016
Author(s)
Ueda T, Nakata Y, Yamasaki N, Oda H, Sentani K, Kanai A, Onishi N, Ikeda K, Sera Y, Honda Z, Tanaka K, Sata M, Ogawa S, Yasui W, Saya H, Takita J, Honda H.
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Journal Title
Oncogene.
Volume: 25
Pages: 4447-4458
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Molecular genetic and cytogenetic analysis of a primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma.2016
Author(s)
Kato K, Oh Y, Takita J, Gunji Y, Kobayashi C, Yoshimi A, Nakao T, Noma M, Koike K, Morimoto A, Iijima S, Hojo H, Tsuchida M.
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Journal Title
Int J Hematol.
Volume: 103
Pages: 196-201
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Genomic analysis of clonal origin of Langerhans cell histiocytosis following acute lymphoblastic leukaemia.2016
Author(s)
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.
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Journal Title
Br J Haematol.
Volume: 175
Pages: 169-172
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Identifications of fatal SPI1fusions and highly aggressive phenotype with SPI1 overexpression in pediatric T cell acute lymphoblastic leukemia/lymphoma2016
Author(s)
Seki M, Kimura S, Yoshida K, Isobe T, Ueno H, Shiozawa Y, Shiraishi Y, Chiba K, Takagi M, Iwama A, Ohki K, Kato M, Koh K, Hanada R, Moritake H, Kobayashi R, Deguchi T, Hashii Y, Imamura T, Sato A, Horibe K, Kiyokawa N, Manabe A, Ohara A, Sanada M, Hayashi Y, Miyano S, Oka A, Ogawa S, Takita J
Organizer
第58回日本小児血液・がん学会学術集会
Place of Presentation
品川プリンスホテル （東京）
Year and Date
2016-12-16
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[Presentation] Integrative genome-wide analysis of pancreatoblastoma2016
Author(s)
Isobe T, Seki M, Yoshida K, Shiraishi Y, Chiba K, Tanaka H, Sato Y, Kataoka K, Suzuki H, Shimamura T, Kawai T, Kato M, Iguchi A, Hama A, Taguchi T, Akiyama M, Fujimura J, Inoue A, Ito T, Deguchi T, Kiyotani C, Yagyu S, Iehara T, Hosoi H, Oka A, Tanaka Y, Hata K, Miyano S, Ogawa S, Takita J
Organizer
第58回日本小児血液・がん学会学術集会
Place of Presentation
品川プリンスホテル （東京）
Year and Date
2016-12-15
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[Presentation] Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcom．2016
Author(s)
Seki M, Nishimura R, Yoshida K, Shimamura T, Shiraishi Y, Sato Y, Kato M, Chiba K, Tanaka H, Hoshino N, Nagae G, Shiozawa Y, Okuno Y, Hosoi H, Tanaka Y, Okita H, Miyachi M, Souzaki R, Taguchi T, Koh K, Hanada R, Kato K, Nomura Y, Akiyama M, Oka A, Igarashi T, Miyano S, Aburatni H, Hayashi Y, Ogawa S, Takita J
Organizer
第58回日本小児血液・がん学会学術集会
Place of Presentation
品川プリンスホテル （東京）
Year and Date
2016-12-15
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[Presentation] Gene Expression Profiles and Methylation Analysis in Down Syndrome Related Acute Lymphoblastic Leukemia2016
Author(s)
Kubota Y, Uryu K, Kawai T, Ito T, Hanada I, Toki T, Seki M, Yoshida K, kataoka K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Oka A, Yasuhide Hayashi Y, Ogawa S, Terui K, Sato A, Hata K, Ito E, Takita J
Organizer
58th ASH Annual Meeting & Exposition
Place of Presentation
San Diego (U.S.A)
Year and Date
2016-12-05
Int'l Joint Research
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[Presentation] Genome-Wide Mutational Landscape of Infant Acute Lymphoblastic Leukemia2016
Author(s)
IsobeＴ, Yoshida K, Kobayashi C, Shiraishi Y, Chiba K, Tanaka H, Fukuda S, Yamamoto S, Tatsuno K, Aoki Y, Miyamura T, Tsutsumi S, Kiyokawa N, Ishihara T, Tomizawa D,Ishii E,Miyano S, Ogawa S, Aburatani H, Mizutani S, Takita J, Takagi M:
Organizer
58th ASH Annual Meeting & Exposition
Place of Presentation
San Diego (U.S.A.)
Year and Date
2016-12-05
Int'l Joint Research
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[Presentation] TAL1 Super Enhancer Aberration and Stil-TAL1 Fusion in Pediatric T Cell Acute Lymphoblastic Leukemia2016
Author(s)
Kimura S, Seki M, Yoshida K,Ueno H, Shiraishi Y, Chiba K, Tanaka H, Suzuki H, Kataoka K, Ohki K, Kato M, Koh K, Hanada R, Kiyokawa N, Kobayashi M, Manabe A, Ohara A, MD, Hayashi Y, Miyano S, Ogawa S, Takita J
Organizer
58th ASH Annual Meeting & Exposition
Place of Presentation
San Diego (U.S.A)
Year and Date
2016-12-05
Int'l Joint Research
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[Presentation] Integrated Genetic and Epigenetic Analysis of Hepatoblastoma2016
Author(s)
Sekiguchi M, Seki M, Isobe M, Hoshino N, Yoshida K, Shiraishi Y, Kawai T, Yoshida M, Chiba K, Tanaka H, Sozaki R, Hata K, Tanaka Y, Taguch T, Miyano S, Hayashi Y, Ogawa S, Takita J
Organizer
Asian Society for Pediatric Research 2016
Place of Presentation
Bangkok (Thailand)
Year and Date
2016-11-10
Int'l Joint Research
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[Presentation] Genome-wide multi-omic analysis of pediatric pancreatoblastom2016
Author(s)
Isobe T, Seki M, Yoshida K, Iguchi A, Hama A, Taguchi T, Tanaka Y,Akiyama M, Fujimura J, Inoue A, Ito T, Deguchi T, Kato M, Kiyotani C, Yagyu S, Iehara T, Hosoi H, Miyano S, Ogawa S, Takita J
Organizer
The 48th Annual Congress of the International Society of Paediatric Oncology
Place of Presentation
Dubline (Ireland)
Year and Date
2016-10-21
Int'l Joint Research
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[Presentation] TAL1 super enhancer aberration and STIL-TAL1 fusion in pediatric T cell acute lymphoblastic leukemia (T-ALL)2016
Author(s)
Kimura S, Seki M, Yoshida K, ShiraishiY, Chiba K, Tanaka H, Suzuki H, Kataoka K, Kato M, Koh K, Hanada R, Imamura T, Kiyokawa N, Hashii Y, Ohara A, Deguchi T, Horibe K, Hayashi Y, Miyano S, Ogawa S, Takita J
Organizer
The 48th Annual Congress of the International Society of Paediatric Oncology
Place of Presentation
Dubline (Ireland)
Year and Date
2016-10-21
Int'l Joint Research
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[Presentation] TAL1 abnormalities in childhood T-Cell acute lymphoblastic leukemia2016
Author(s)
Seki M, Yoshida K, Kimura S, Isobe T, ShiraishiY, Kato M, Koh K, Hanada R, DeguchiT, Imamura T, Horibe K, Kiyokawa N, Manabe A, Ohara A, Sanada M, Mano H, HayashiY, Miyano S, Oka A, Ogawa S, Takita J
Organizer
The 48th Annual Congress of the International Society of Paediatric Oncology
Place of Presentation
Dubline (Ireland)
Year and Date
2016-10-19
Int'l Joint Research
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[Presentation] Identifications of novel recurrent SP11 fusions in highly aggressive phenotype of pediatric T-ALL2016
Author(s)
Seki M, Yoshida K, Kimura S, Ueno H, Shiraishi Y, Takagi M, Iwama A, Kataoka K, Shiozawa Y, Kato M, Moritake H, Koh K, Hanada R, Hashii Y, Deguchi T, Kobayashi R, Sato A, Imamura T, Horibe K, Ohki K, Kiyokawa N, Manabe A, Ohara A, Sanada M, Mano H, Oka A, Miyano S, Hayashi Y, Ogawa S, Takita J
Organizer
第78回日本血液学会学術集会
Place of Presentation
パシフィコ横浜 (横浜）
Year and Date
2016-10-13
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[Presentation] Clustering analysis on gene expression data of pediatric hepatoblastoma2016
Author(s)
Sekiguchi M, Seki M, Hoshino N, Yoshida K, Shiraishi Y, Yoshida M, Souzaki R, Tanaka Y, Taguchi T, Miyano S, Hayashi Y, Ogawa S, Takita J
Organizer
第75回日本癌学会学術総会
Place of Presentation
パシフィコ横浜 (横浜）
Year and Date
2016-10-08
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[Presentation] Mutation analysis of NOTCH1and FBXW7 in pediatric T cell acute lymphoblastic leukemia (T-ALL)2016
Author(s)
Kimura S, Seki M, Yoshida K, Shiraishi Y, Chiba K, Tanaka H, Akiyama M, Koh K, Miyano S, Imamura T, Ogawa S, Takita J
Organizer
第75回日本癌学会学術総会
Place of Presentation
パシフィコ横浜 (横浜）
Year and Date
2016-10-07
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[Presentation] Genetic characteristic of 500 neuroblastomas using genomewide combined with immunohistochemistry2016
Author(s)
Uryu K, Yoshida K, Kataoka K, Seki M, Hiwatari M, Hayashi Y, Nakazawa A, Takimoto T, Tajiri T, Nakagawara A, Miyano S, Ogawa S, Takita J
Organizer
第75回日本癌学会学術総会
Place of Presentation
パシフィコ横浜 (横浜）
Year and Date
2016-10-06
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[Presentation] DNA methylation analysis in acute lymphoblatic leukemia of Down syndrome2016
Author(s)
Kubota Y, Uryu K, Kawai T, Ito T, Hanada I, Toki T, Seki M, Yoshida K, Sato Y, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Oka A, Hayashi Y, Ogawa S, Terui K, Sato A, Hata K, Ito E, Takita J
Organizer
The 35th Sapporo International Cancer Symposium 2016
Place of Presentation
ロイトン札幌 （札幌）
Year and Date
2016-06-24
Int'l Joint Research
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[Presentation] Genetic characteristics of 494 neuroblastomas using genome-wide analysis combined with immunohistochemistry2016
Author(s)
Uryu K, Nishimura R, Yoshida K, Kataoka K, Shiraishi Y, Chiba K , Tanaka H, Seki M , Hoshino N, Hiwatari M, Oka A, Hayashi Y, Nakazawa A, Takimoto T, Tajiri T, Nakagawara A, Miyano S, Ogawa S, Takita J
Organizer
Advances in Neuroblastoma Research
Place of Presentation
Cairns (Australia)
Year and Date
2016-06-20
Int'l Joint Research
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