2015 Fiscal Year Annual Research Report
包括的ゲノムスキャンニングによる小児がんと先天奇形症候群の新規治療戦略の開発
Project/Area Number |
26670493
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Research Institution | The University of Tokyo |
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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Project Period (FY) |
2014-04-01 – 2016-03-31
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Keywords | 神経芽腫 / 横紋筋肉腫 / Ewing肉腫 / 発達障害 / 自閉症 / 次世代シークエンサー / エクソーム解析 |
Outline of Annual Research Achievements |
発達障害と腫瘍発生の双方に関与する分子病態を解明するために、広汎性発達障害と神経芽腫を併発した例(症例1)、重度の精神発達障害を合併した横紋筋肉腫の例(症例2)、自閉症にEwing肉腫を合併した例(症例3)の正常および腫瘍検体を用いて、exome解析を行った。 症例1では、腫瘍細胞特異的なsomatic変異は初発検体で5個、再発検体で32個検出された。初発、再発腫瘍で共通する変異はALK変異のみであった。本症例特有のgermline変異は約300個検出されたが、家族性のミオクローヌス癲癇の原因遺伝子と考えられるCSMD2の変異が含まれていた。興味深いことに、腫瘍検体においてこの遺伝子の欠失が確認され、その機能喪失が腫瘍化に関与している可能性が示された。 症例2では、腫瘍細胞に特異的なsomatic変異は初発検体で9個、再発検体で24個検出された。本症例に特異的なgermline変異は約450個検出された。この中に神経発達に関与する接着分子であるCNTN6が含まれていた。この遺伝子は自閉症の発症に関与することが知られており、また卵巣がんなどではがん抑制遺伝子と考えられている。以上の結果より、CSMD2およびCNTN6の異常は、自験例において発達障害と腫瘍発生の双方に関与する標的分子の一つである可能性が示唆された。 症例3の対照として正常児に発症したEwing肉腫2例も同時に解析した(症例4,5)。症例3では、悪性黒色腫で検出されたがん抑制遺伝子、体細胞変異を見出した。Grmline変異として、神経の分化に関与する遺伝子の変異と神経系で強く発現する転写因子の変異を検出した。これらの変異は対照症例では、検出されなかった。以上の結果より、Ewing肉腫と自閉症には、神経系の分化や転写に関与する遺伝子異常が発症に関与している可能性が示唆された。
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Research Products
(51 results)
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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: -
Pages: -
DOI
Peer Reviewed / Open Access
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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, and Oda M.
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Journal Title
J Hum Genet
Volume: -
Pages: -
DOI
Peer Reviewed / Open Access
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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, and Honda H.
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Journal Title
Oncogene
Volume: -
Pages: -
DOI
Peer Reviewed / Open Access
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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
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[Journal Article] Genomic analysis of clonal origin of Langerhans cell histiocytosis following acute lymphoblastic leukaemia.2015
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: -
Pages: -
DOI
Peer Reviewed / Open Access
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[Journal Article] Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma.2015
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, Aburatani H, Hayashi Y, Ogawa S, Takita J.
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Journal Title
Nat. Commun.
Volume: 3;6
Pages: 7557
DOI
Peer Reviewed / Open Access
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[Journal Article] A case of atypical dyskeratosis congenita presenting as myelodysplastic syndrome and genetically diagnosed using whole-exome sequencing.2015
Author(s)
Monoi A, Sugawa M, Kato M, Seki M, Watanabe K, Yoshida K, Sakaguchi H, Hama A, Ogawa S, Oka A, Takita J.
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Journal Title
Oncology Lett.
Volume: -
Pages: -
DOI
Peer Reviewed / Open Access
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[Journal Article] Comparison of chemotherapeutic agents as a myeloablative conditioning with TBI for pediatric ALL: a study from the pediatric ALL working group of the JSHCT.2015
Author(s)
Kato M, Ishida H, Koh K, Inagaki J, Kato K, Goto H, Kaneko T, Cho Y, Hashii Y, Kurosawa H, Takita J, Hamamoto K, Inoue M, Sawada A, Suzuki R, Kato K.
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Journal Title
Pediatr Blood Cancer.
Volume: 62
Pages: 1844-50
DOI
Peer Reviewed / Open Access
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[Journal Article] Upregulation of MAPK negative feedback regulators and RET in mutant ALK neuroblastoma: implications for targeted treatment.2015
Author(s)
Lambertz I, Kumps C, Claeys S, Lindner S, Beckers A, Janssens E, Carter DR, Cazes A, Cheung BB, De Mariano M, De Bondt A, De Brouwer S, Delattre O, Gibbons J, Janoueix-Lerosey I, Laureys G, Liang C, Marshall GM, Porcu M, Takita J et all.
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Journal Title
Clin Cancer Res.
Volume: 21
Pages: 3327-39
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Aggressive transformation of anaplastic large cell lymphoma with increased number of ALK-translocated chromosomes.2015
Author(s)
Hoshino A, Nomura K, Hamashima T, Isobe T, Seki M, Hiwatari M, Yoshida K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Takita J, Kanegane H.
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Journal Title
Int J Hematol.
Volume: 101
Pages: 198-202
DOI
Peer Reviewed / Open Access
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[Journal Article] Allogeneic haematopoietic stem cell transplantation for infant acute lymphoblastic leukaemia with KMT2A (MLL) rearrangements: a retrospective study from the paediatric acute lymphoblastic leukaemia working group of the Japan Society for Haematopoietic Cell Transplantation.2015
Author(s)
Kato M, Hasegawa D, Koh K, Kato K, Takita J, Inagaki J, Yabe H, Goto H, Adachi S, Hayakawa A, Takeshita Y, Sawada A, Atsuta Y, Kato K.
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Journal Title
Br J Haematol.
Volume: 168
Pages: 564-70
DOI
Peer Reviewed / Open Access
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[Journal Article] Early use of allogeneic hematopoietic stem cell transplantation for infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia.2015
Author(s)
Koh K, Tomizawa D, Moriya Saito A, Watanabe T, Miyamura T, Hirayama M, Takahashi Y, Ogawa A, Kato K, Sugita K, Sato T, Deguchi T, Hayashi Y, Takita J, Takeshita Y, Tsurusawa M, Horibe K, Mizutani S, Ishii E.
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Journal Title
Leukemia.
Volume: 29
Pages: 290-6
DOI
Peer Reviewed / Open Access
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[Journal Article] Identification of a homozygous JAK3 V674A mutation caused by acquired uniparental disomy in a relapsed early T-cell precursor ALL patient.2015
Author(s)
Kawashima-Goto S, Imamura T, Seki M, Kato M, Yoshida K, Sugimoto A, Kaneda D, Fujiki A, Miyachi M, Nakatani T, Osone S, Ishida H, Taki T, Takita J, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Hosoi H.
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Journal Title
Int J Hematol.
Volume: 101
Pages: 411-6
DOI
Peer Reviewed / Open Access
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[Presentation] TAL1 and MYB Abnormalities in Childhood T-Cell Acute Lymphoblastic Leukemia.2015
Author(s)
Seki M, Yoshida K, Shiraishi Y, Chiba K, Tanaka H, Kato M, Kimura S, Hanada R, Koh K, Miyano S, Imamura T, Horibeb K, Kiyokawa N, Manabe A, Ohara A, Hayashi Y, Oka A, Ogawa S, Takita J
Organizer
57th American Society of Hematology Annual Meeting
Place of Presentation
San Diego, U.S.A.
Year and Date
2015-12-05 – 2015-12-08
Int'l Joint Research
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[Presentation] Genetic characterization of ALK positive neuroblastoma using genome-wide analysis combined with immunohistochemistry.2015
Author(s)
Uryu K, Nishimura R, Yoshida K, Seki M, Hoshino N, Kato M, Hiwatari M, Oka A, Hayashi Y, Nakazawa A, Tajiri T, Nakagawara A, Miyano S, Ogawa S, Takita J
Organizer
第57回日本小児血液・がん学会学術集会
Place of Presentation
山梨
Year and Date
2015-11-27 – 2015-11-29
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[Presentation] A comparison of the genetic feature in Down syndrome-ALL and non-Down syndrome-ALL.2015
Author(s)
Uryu K, Yoshida K, Sek M, Hoshino N, Kato M, Hiwatari M, Oka A, Ogawa S, Miyano S, Kikuchi A, Takita J
Organizer
第57回日本小児血液・がん学会学術集会
Place of Presentation
山梨
Year and Date
2015-11-27 – 2015-11-29
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[Presentation] Identification of subgroup of pediatric ALL who can and cannot be cured by short maintenance therapy.2015
Author(s)
Kato M,Manabe A, Ishimaru S, Seki M, Yoshida K, Sato Y, Tomizawa D, Hasegawa D, Inukai T, Arakawa Yi, Aoki T, Okuya M, Kaizu K, Kato K, Taneyama Y, Takita J, Ogawa Si, Koh K, Tsuchida M, Ohara A
Organizer
第57回日本小児血液・がん学会学術集会
Place of Presentation
山梨
Year and Date
2015-11-27 – 2015-11-29
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[Presentation] 膵芽腫におけるゲノム異常を特徴付ける11p15.5ヘテロ接合生喪失とCTNNB1体細胞変異.2015
Author(s)
関正史, 磯部知哉, 吉田健一, 白石友一, 千葉健一, 田中洋子, 佐藤悠介, 加藤元博, 井口晶裕, 濱麻人, 宗崎良太, 田口智章, 田中祐吉, 秋山政晴, 藤村純也, 井上彰子, 伊藤剛, 出口隆生, 宮野悟, 小川誠司, 滝田順子
Organizer
第57回日本小児血液・がん学会学術集会
Place of Presentation
山梨
Year and Date
2015-11-27 – 2015-11-29
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[Presentation] 甲状腺濾胞癌の発生を契機に生殖細胞のDICER1遺伝子異常を同定した2症例.2015
Author(s)
吉田美沙, 村岡枝里香, 関正史, 吉田健一, 浜之上聡, 武山絵里子, 田中水緒, 後藤裕明, 宮野悟, 小川誠司, 滝田順子, 田中祐吉
Organizer
第57回日本小児血液・がん学会学術集会
Place of Presentation
山梨
Year and Date
2015-11-27 – 2015-11-29
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[Presentation] Whole exome and transcriptome analyses in pediatric T-cell acute lymp hoblastic leukemia2015
Author(s)
Seki M, Yoshida K, Shiraishi Y, Chiba K, Tanaka H, Kato M, Imamura T, Hanada R, Miyano S, Hayashi Y, Ogawa S, Takita J
Organizer
第77回日本血液学会学術集会
Place of Presentation
金沢
Year and Date
2015-10-16 – 2015-10-18
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[Presentation] Integrated genetic and epigenetic analysis defines novel molecular clusters in rhabdomyosarcoma.2015
Author(s)
Seki M, Nishimura R, Yoshida K, Shimamura T, Shiraishi Y, Sato Y, Kato M, Chiba K, Tanaka H, Nagae G, Okuno Y, Hoso H, Tanaka Y, Ohkita H, Miyashi M, Taguchi T, Koh K, Hanada R, Oka A, Miyano S, Aburatani H, Hayashi Y, Ogawa S, Takita J
Organizer
American Association for Cancer Research 2015
Place of Presentation
Pensylvania, U.S,A,
Year and Date
2015-04-18 – 2015-04-22
Int'l Joint Research
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[Presentation] Clonal evolution and integral analysis of hepatoblastoma.2015
Author(s)
Hoshino N, Seki M, Kato M, Yoshida K, Sato Y, Nakazawa A, Miyano S, Oka A, Iwanaka T, Hayashi Y, Ogawa S, Takita J
Organizer
American Association for Cancer Research 2015
Place of Presentation
Pensylvania, U.S,A,
Year and Date
2015-04-18 – 2015-04-22
Int'l Joint Research
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[Presentation] The Genetic landscape of neuroblastoma.2015
Author(s)
Uryu K, Nishimura R, Yoshida K, Seki M, Kato M, Oka A, Hayashi Y, Tajiri T, Nakagawara A, Ogawa S, Takita J
Organizer
The 11th Asian Society for Pediatric Research
Place of Presentation
Osaka
Year and Date
2015-04-15 – 2015-04-18
Int'l Joint Research
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[Presentation] Integrated genetic and epigenetic analysis in rhabdomyosarcoma.2015
Author(s)
Seki M, Yoshida K, Hosoi H, Tanaka Y, Okita H, Hanada R, Igarashi T, Oka A, Hayahshi Y, Ogawa S, Takita J:
Organizer
The 11th Asian Society for Pediatric Research
Place of Presentation
Osaka
Year and Date
2015-04-15 – 2015-04-18
Int'l Joint Research
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[Presentation] Genetic alterations in ATM pathway related genes in neuroblastoma.2015
Author(s)
Yoshida M, Kato M, Uryu K, Hoshino N, Seki M, Hiwatari M, Yoshida K, Oka A, Ogawa S, Hayashi Y, Takita J
Organizer
The 11th Asian Society for Pediatric Research
Place of Presentation
Osaka
Year and Date
2015-04-15 – 2015-04-18
Int'l Joint Research
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[Presentation] Clonal evolution and pathology in hepatoblastoma with familial adenomatous polyposis.2015
Author(s)
Hoshino N, Seki M, Yoshida K, Kato M, Sato Y, Nakagawa A, Miyano S, Iwanaka T, Oka A, Ogawa S, Takita J
Organizer
The 11th Asian Society for Pediatric Research
Place of Presentation
Osaka
Year and Date
2015-04-15 – 2015-04-18
Int'l Joint Research
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