Exploring the role of methylation and hydroxymethylation in Hereditary Breast and Ovarian Cancer

• Project/Area Number: 15K15478
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: 独立行政法人国立病院機構(東京医療センター臨床研究センター)
• Principal Investigator: Yamazawa Kazuki 独立行政法人国立病院機構(東京医療センター臨床研究センター), その他部局等, 医師 (10338113)
• Co-Investigator(Kenkyū-buntansha): 松永 達雄 独立行政法人国立病院機構(東京医療センター臨床研究センター), 聴覚平衡覚研究部, 部長 (90245580)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 遺伝性乳癌卵巣癌 / 遺伝性腫瘍 / メチル化 / ヒドロキシメチル化 / エピジェネティクス / 遺伝性乳がん・卵巣がん症候群

Outline of Final Research Achievements

The novel method to analyze the distribution of methylation/hydroxymethylation in genomic DNA has been developed. Using this method, we first reported the hydroxymethylation status in congenital human imprinting disorders. Next, we have tried to analyze the blood and tumor samples derived from the hereditary tumor syndromes; however, a limited number of tumor samples and denaturation of DNA have created much difficulties in performing the analysis. It has taken more time than expected to re-collect and re-analyze human tumor samples, thus the investigation has yet to be completed. We are still conducting the analysis.

Research Products

• [Int'l Joint Research] University of Cambridge/Babraham Institute(英国)
• [Int'l Joint Research] University of Cambridge/Babraham Institute(英国)
• [Journal Article] High-level heteroplasmy for the m.7445A>G mitochondrial DNA mutation can cause progressive sensorineural hearing loss in infancy. (2018)
  • Author(s): Matsushima K, Nakano A, Arimoto Y, Mutai H, Yamazawa K, Murayama K, Matsunaga T.
  • Journal Title: Intl J Ped Otorhinolaryng Volume: 108 Pages: 125-131
  • DOI: 10.1016/j.ijporl.2018.02.037
  • Peer Reviewed
• [Journal Article] 起立性低血圧症状で発症した自己免疫性自律神経節障害の9歳児例． (2018)
  • Author(s): 2.河津桃子，三春晶嗣，鳥井健一，雨宮あつこ，鈴木絵理，山澤一樹，藤田尚代，込山修，樋口理，中根俊成，小平隆太郎，高橋孝雄．
  • Journal Title: 小児科臨床 Volume: 71 Pages: 47-53
• [Journal Article] Spontaneous intramural duodenal hematoma as the manifestation of Noonan syndrome. (2018)
  • Author(s): Yamazawa K, Yamada Y, Kuroda T, Mutai H, Matsunaga T, Komiyama O, Takahashi T.
  • Journal Title: Am J Med Genet A Volume: 176 Issue: 2 Pages: 496-498
  • DOI: 10.1002/ajmg.a.38556
  • Peer Reviewed
• [Journal Article] 単為生殖とゲノムワイド片親性ダイソミー. (2017)
  • Author(s): 山澤一樹
  • Journal Title: 医学のあゆみ Volume: 263 Pages: 317-321
• [Journal Article] Genetic heterogeneity of patients with suspected Silver-Russell syndrome: genome-wide copy number analysis in 82 patients without imprinting defects. (2017)
  • Author(s): Inoue T, Nakamura A, Fuke T, Yamazawa K, Sano S, Matsubara K, Mizuno S, Matsukura Y, Harashima C, Hasegawa T, Nakajima H, Tsumura K, Kizaki Z, Oka A, Ogata T, Fukami M, Kagami M.
  • Journal Title: Clin Epigenetics Volume: 9 Issue: 1 Pages: 52-52
  • DOI: 10.1186/s13148-017-0350-6
  • Peer Reviewed / Open Access
• [Journal Article] H1foo Has a Pivotal Role in Qualifying Induced Pluripotent Stem Cells (2016)
  • Author(s): Kunitomi A, Yuasa S, Sugiyama F, Saito Y, Seki T, Kusumoto D, Kashimura S, Takei M, Tohyama S, Hashimoto H, Egashira T, Tanimoto Y, Mizuno S, Tanaka S, Okuno H, Yamazawa K, Watanabe H, Oda M, Kaneda R, Matsuzaki Y, Nagai T, Okano H, Yagami K, Tanaka M, Fukuda K.
  • Journal Title: Stem Cell Reports Volume: 6 Issue: 6 Pages: 825-833
  • DOI: 10.1016/j.stemcr.2016.04.015
  • NAID: 120007135348
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ゲノム時代の到来と遺伝リテラシー (2016)
  • Author(s): 山澤一樹
  • Journal Title: 国立医療学会誌 Volume: 70 Pages: 106-109
  • Peer Reviewed
• [Journal Article] Exploration of hydroxymethylation in Kagami-Ogata syndrome caused by hypermethylation of imprinting control regions. (2015)
  • Author(s): Matsubara K, Kagami M, Nakabayashi K, Hata K, Fukami M, Ogata T, Yamazawa K.
  • Journal Title: Clin Epigenetics Volume: 28;7(1) Issue: 1 Pages: 90-90
  • DOI: 10.1186/s13148-015-0124-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression (2015)
  • Author(s): Ruslan Strogantsev, Felix Krueger, Kazuki Yamazawa, Hui Shi, Poppy Gould, Megan Goldman-Roberts, Kirsten McEwen, Bowen Sun, Roger Pedersen, Anne C. Ferguson-Smith
  • Journal Title: Genome Biology Volume: 16 Issue: 1 Pages: 112-112
  • DOI: 10.1186/s13059-015-0672-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 今月の用語 次世代シークエンサー (2015)
  • Author(s): 山澤一樹
  • Journal Title: 国立医療学会誌 Volume: 69 Pages: 383-383
  • Peer Reviewed
• [Presentation] SMAD4遺伝子に病的バリアントを同定した若年性ポリポーシス/遺伝性出血性末梢血管拡張症症候群家系 (2018)
  • Author(s): 山澤一樹、安達将隆、國富晴子、増田健太、石田文孝、三須久美子、小崎健次郎、浜本康夫、後藤修、矢作直久、牛尼美年子、吉田輝彦、菅野康吉
  • Organizer: 第24回日本家族性腫瘍学会
• [Presentation] 臨床的観点からみたジェネティクスとエピジェネティクス (2018)
  • Author(s): 山澤一樹
  • Organizer: 第3回三重NICUフォローアップ検討会
  • Invited
• [Presentation] 東京医療センター・臨床遺伝センターの歩み (2018)
  • Author(s): 山澤一樹
  • Organizer: Ophthalmic Genetics Meeting 2018
  • Invited
• [Presentation] CDC73遺伝子の生殖細胞系列における全欠失および体細胞系列における病的バリアントを同定した原発性副甲状腺機能亢進症の男児例． (2018)
  • Author(s): 山澤一樹，籏生なおみ，香取奈穂，前田直則，鈴木絵理，込山修，筒井英光，長尾俊孝，佐藤武志，石井智弘，長谷川奉延．
  • Organizer: 第40回日本小児遺伝学会
• [Presentation] Germline whole-gene deletion and somatic nonsense variant of the CDC73 gene in a boy with primary hyperparathyroidism. (2017)
  • Author(s): Hatabu N, Katori N, Maeda N, Suzuki E, Komiyama O, Tsutsui H, Nagao T, Sato T, Ishii T, Hasegawa T, Yamazawa K.
  • Organizer: 日本人類遺伝学会第62回大会
• [Presentation] メチル化異常に起因する小児先天異常症候群においてヒドロキシメチル化が果たす役割の解明． (2017)
  • Author(s): 山澤一樹
  • Organizer: 第51回日本小児内分泌学会
• [Presentation] CDC73遺伝子全領域を含む3.4 Mbの欠失を認めた副甲状腺腺腫の15歳男児例. (2017)
  • Author(s): 山澤一樹, 前田直則, 籏生なおみ, 香取奈穂, 鈴木絵理, 込山修, 佐藤武志, 石井智弘, 長谷川奉延, 筒井英光, 長尾俊孝.
  • Organizer: 第23回日本家族性腫瘍学会
• [Presentation] 山澤一樹, 込山修, 高橋孝雄. 非典型的表現型により未診断のまま重篤な出血エピソードを繰り返したヌーナン症候群の一例. (2017)
  • Author(s): 山澤一樹, 込山修, 高橋孝雄.
  • Organizer: 第120回日本小児科学会
• [Presentation] 2回の重篤な出血のエピソードを認め、エクソーム解析によって診断されたヌーナン症候群の一例 (2016)
  • Author(s): 山澤一樹, 山田洋平, 務台英樹, 松永達雄, 込山修, 高橋孝雄
  • Organizer: 第39回日本小児遺伝学会学術集会
  • Place of Presentation: 慶應義塾大学三田キャンパス（東京都港区）
  • Year and Date: 2016-12-09
• [Presentation] 遺伝性乳がん・卵巣がんの診療の実情 (2016)
  • Author(s): 山澤一樹
  • Organizer: 乳がん地域医療を考える会
  • Place of Presentation: セルリアンタワー東急ホテル（東京都渋谷区）
  • Year and Date: 2016-05-25
  • Invited
• [Presentation] Exploration of hydroxymethylation in Kagami-Ogata syndrome caused by hypermethylation of imprinting control regions (2016)
  • Author(s): Yamazawa K, Matsubara K, Kagami M, Nakabayashi K, Hata K, Fukami M, Ogata T
  • Organizer: International Congress of Human Genetics 2016 Annual Meeting
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] インプリンティング調節領域の高メチル化に起因したKagami-Ogata症候群におけるヒドロキシメチル化の探索 (2015)
  • Author(s): 山澤一樹、松原圭子、鏡雅代、中林一彦、秦健一郎、深見真紀、緒方勤
  • Organizer: 日本人類遺伝学会第60回大会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-10-15
• [Presentation] Exploration of hydroxymethylation in Kagami-Ogata syndrome caused by hypermethylation of imprinting control regions (2015)
  • Author(s): Kazuki Yamazawa, Keiko Matsubara, Masayo Kagami, Kazuhiko Nakabayashi, Kenichiro Hata, Maki Fukami, Tsutomu Ogata
  • Organizer: ASHG 2015 Annual Meeting
  • Place of Presentation: Baltimore Convention Center (Baltimore, MD, USA)
  • Year and Date: 2015-10-11
  • Int'l Joint Research
• [Presentation] IG-DMRの高メチル化に起因するKagami-Ogata症候群におけるヒドロキシメチル化の探索 (2015)
  • Author(s): 山澤一樹、松原圭子、鏡雅代、中林一彦、深見真紀、緒方勤
  • Organizer: 第49回日本小児内分泌学会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-10-09
• [Presentation] メチル化異常に起因するKagami-Ogata症候群においてヒドロキシメチル化の果たす役割の解明 (2015)
  • Author(s): 山澤一樹、松原圭子、鏡雅代、深見真紀、中林一彦、緒方勤
  • Organizer: 第38回小児遺伝学会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2015-07-25
• [Presentation] メチル化異常に起因する小児先天異常症候群においてヒドロキシメチル化が果たす役割 (2015)
  • Author(s): 山澤一樹
  • Organizer: 第118回日本小児科学会
  • Place of Presentation: 大阪国際会議場（大阪市）
  • Year and Date: 2015-04-18