最適な乳がんホルモン療法を患者に届けるための新たな遺伝子診断法の開発

• Project/Area Number: 18K07310
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: 前佛 均 公益財団法人がん研究会, がんプレシジョン医療研究センター リキッドバイオプシー診断開発プロジェクト, プロジェクトリーダー(部長クラス) (90372820)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Discontinued (Fiscal Year 2019)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 乳癌 / エクソーム / ターゲットリシークエンス / ホルモン療法 / タモキシフェン / 副作用 / 有効性 / 内分泌治療 / 遺伝子診断

Outline of Annual Research Achievements

令和元年度はタモキシフェンを含む乳がんホルモン療法が施行された患者を対象に血液サンプルの単核球分画より、生殖細胞系列のゲノムDNAを抽出し、エクソーム解析を行った。average depth of coverageは50程度であり、HGVD(Human Genome Variation Database)のreference配列と各症例のゲノムシーケンスを比較したところ、各症例につき約12万個のSingle Nucleotide Variant (SNV),Insertion/Deletion多型が同定された。同じくHGVDのreference配列をコントロールとしてC10orf11のターゲット・リシークエンスも行ったところ、0.1程度のアレル頻度をもつバリアント(SNV)を同定した。
また昨年度に引き続き、本研究対象となる、上記治療を受けた乳がん症例を電子カルテより検索し、① 基本情報 (年齢、性別、がん種、既往歴、現病歴、家族歴、病期、治療内容、予後等)、②本研究に必要な情報 (前治療内容、治療開始日、投与量、併用薬剤、投与期間、投与方法、投与経路、副作用情報 (種類、発現日、Grade、発現期間等)、治療反応性情報 (縮小率、無再発生存期間、生存期間、無増悪生存期間等)) 等を抽出し、本研究における解析用の臨床情報データベースの一部を構築した。

Research Products

• [Journal Article] Serial circulating tumour DNA analysis for locally advanced rectal cancer treated with preoperative therapy: prediction of pathological response and postoperative recurrence (2020)
  • Author(s): Murahashi Satoshi、Akiyoshi Takashi、Sano Takeshi、Fukunaga Yosuke、Noda Tetsuo、Ueno Masashi、Zembutsu Hitoshi
  • Journal Title: Br J Cancer Volume: - Pages: 803-810
  • DOI: 10.1038/s41416-020-0941-4
  • Peer Reviewed
• [Journal Article] Liquid biopsy for the detection of clinical biomarkers in early breast cancer: new insights and challenges (2020)
  • Author(s): Matsutani Akiko、Udagawa Chihiro、Matsunaga Yuki、Nakamura Seigo、Zembutsu Hitoshi
  • Journal Title: Pharmacogenomics Volume: 21 Pages: 359-367
  • DOI: 10.2217/pgs-2019-0130
  • Peer Reviewed
• [Journal Article] Early change in circulating tumor DNA as a potential predictor of response to chemotherapy in patients with metastatic colorectal cancer (2019)
  • Author(s): Osumi Hiroki、Shinozaki Eiji、Yamaguchi Kensei、Zembutsu Hitoshi
  • Journal Title: Scientific Reports Volume: 9
  • DOI: 10.1038/s41598-019-53711-3
  • Peer Reviewed / Open Access
• [Journal Article] A Genome-Wide Association Study Identifies Five Novel Genetic Markers for Trastuzumab-Induced Cardiotoxicity in Japanese Population (2019)
  • Author(s): Nakano Mari Hara、Udagawa Chihiro、Shimo Arata、Kojima Yasuyuki、Yoshie Reiko、Zaha Hisamitsu、Abe Norie、Motonari Tokiwa、Unesoko Mikiko、Tamura Kenji、Shimoi Tatsunori、Yoshida Masayuki、Yoshida Teruhiko、Sakamoto Hiromi、Kato Ken、Mushiroda Taisei、Tsugawa Koichiro、Zembutsu Hitoshi
  • Journal Title: Biol. Pharm. Bull. Volume: 42 Issue: 12 Pages: 2045-2053
  • DOI: 10.1248/bpb.b19-00527
  • NAID: 130007754507
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access
• [Journal Article] Whole genome sequencing to identify predictive markers for the risk of drug-induced interstitial lung disease (2019)
  • Author(s): Udagawa Chihiro、Horinouchi Hidehito、Shiraishi Kouya、Kohno Takashi、Okusaka Takuji、Ueno Hideki、Tamura Kenji、Ohe Yuichiro、Zembutsu Hitoshi
  • Journal Title: PLOS ONE Volume: 14
  • DOI: 10.1371/journal.pone.0223371
  • Peer Reviewed / Open Access
• [Journal Article] Clinical utility of circulating tumor DNA for colorectal cancer (2019)
  • Author(s): Osumi Hiroki、Shinozaki Eiji、Yamaguchi Kensei、Zembutsu Hitoshi
  • Journal Title: Cancer Science Volume: 110 Pages: 1148-1155
  • DOI: 10.1111/cas.13972
  • Peer Reviewed / Open Access
• [Journal Article] Clinical relevance of circulating tumor DNA assessed through deep sequencing in patients with metastatic colorectal cancer (2019)
  • Author(s): Osumi Hiroki、Shinozaki Eiji、Takeda Yoshinori、Wakatsuki Takeru、Ichimura Takashi、Saiura Akio、Yamaguchi Kensei、Takahashi Shunji、Noda Tetsuo、Zembutsu Hitoshi
  • Journal Title: Cancer Medicine Volume: 8 Pages: 408-417
  • DOI: 10.1002/cam4.1913
  • Peer Reviewed / Open Access
• [Journal Article] A prospective study to examine the accuracies and efficacies of prediction systems for response to neoadjuvant chemotherapy for muscle invasive bladder cancer. (2018)
  • Author(s): Kato Y, Zembutsu H, Takata R, Matsuura T, Kato R, Kanehira M, Iwasaki K, Yamada N, Katagiri T, Sugai T, Fujioka T, Nakamura Y, Obara W.
  • Journal Title: Oncology Letters Volume: 16 Pages: 5775-5784
  • DOI: 10.3892/ol.2018.9330
  • NAID: 120007099372
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A genome-wide association study identifies three novel genetic markers for response to tamoxifen: A prospective multicenter study (2018)
  • Author(s): Onishi Hiroshi、Udagawa Chihiro、Kubo Michiaki、Nakamura Seigo、Akashi-Tanaka Sadako、Kuwayama Takashi、Watanabe Chie、Endo Itaru、Zembutsu Hitoshi, et all.
  • Journal Title: PLOS ONE Volume: 13
  • DOI: 10.1371/journal.pone.0201606
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] がんプレシジョン医療を目指したリキッドバイオプシー技術の臨床応用 (2018)
  • Author(s): 前佛均
  • Journal Title: 外科 Volume: 80 Pages: 1200-1204
• [Presentation] Early change in circulating tumor DNA as a potential predictor of response to chemotherapy in patients with metastatic (2020)
  • Author(s): Hitoshi Zembutsu、Hiroki Osumi、Eiji Shinozaki、Kensei Yamaguchi
  • Organizer: Advances in Liquid Biopsies
  • Int'l Joint Research
• [Presentation] 大腸がんにおける循環腫瘍細胞DNAの早期量的変化は化学療法有効性の予測マーカーとなり得る (2019)
  • Author(s): 前佛均、大隅寛木、篠崎英司、山口研成
  • Organizer: 日本人類遺伝学会第64回大会
• [Presentation] Whole genome sequencing to identify predictive marker for the risk of drug-induced interstitial lung disease. (2019)
  • Author(s): H. Zembutsu、C. Udagawa、H. Horinouchi、K. Shiraishi、T. Kohno、T. Okusaka、H. Ueno、K. Tamura、Y. Ohe.
  • Organizer: ASHG 2019 Annual Meeting
  • Int'l Joint Research
• [Presentation] 大腸がんにおける循環腫瘍細胞DNAの早期量的変化は化学療法有効性の予測マーカーとなり得る (2019)
  • Author(s): 前佛均、大隅寛木、篠崎英司、山口研成
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] Circulating tumor DNA assessed through amplicon-based next-generation sequencing and its clinical application. (2019)
  • Author(s): Hitoshi Zembutsu, Hiroki Osumi, Eiji Shinozaki, Kensei Yamaguchi, Masato Ozaka, Takashi Sasaki, Marie Muramatsu, Naoki Sasahira.
  • Organizer: AACR Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] Clinical relevance of circulating tumor DNA assessed through amplicon-based next-generation sequencing. (2019)
  • Author(s): Hitoshi Zembutsu, Hiroki Osumi, Eiji Shinozaki, Kensei Yamaguchi, Masato Ozaka, Takashi Sasaki, Naoki Sasahira.
  • Organizer: 11th AACR-JCA Joint Conference
  • Int'l Joint Research
• [Presentation] Clinical relevance of circulating tumor DNA assessed through amplicon-based next-generation sequencing in cancer. (2018)
  • Author(s): Hitoshi Zembutsu, Hiroki Osumi, Kensei Yamaguchi, Eiji Shinozaki, Masato Ozaka, Takashi Sasaki, Naoki Sasahira.
  • Organizer: ASHG Annual meeting 2018
  • Int'l Joint Research
• [Presentation] cfDNAパネルを用いたctDNA検出の臨床実用性の検討 (2018)
  • Author(s): 前佛均
  • Organizer: 第63回日本人類遺伝学会
• [Presentation] cfDNAパネルを用いたctDNA検出の臨床実用性の検証 (2018)
  • Author(s): 前佛均
  • Organizer: 第77回日本癌学会学術総会
  • Invited
• [Book] プレシジョン・メディシン : ビッグデータの構築・分析から臨床応用・課題まで (2018)
  • Author(s): 松原 謙一、榊 佳之、佐藤 孝明
  • Total Pages: 406
  • Publisher: エヌ・ティー・エス
  • ISBN: 9784860435806