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Analysis of intra-tumoral heterogeneity of breast cancer using single-cell whole-genome sequencing techniques(Fostering Joint International Research)

Research Project

Project/Area Number 16KK0204
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field General surgery
Research InstitutionNagasaki University

Principal Investigator

OIKAWA Masahiro  長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (90612416)

Research Collaborator Navin Nicholas  The University of Texas MD Anderson Cancer Center, The Department of Genetics, Associate Professor
Project Period (FY) 2016 – 2018
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Keywords乳がん / リキッドバイオプシー / 腫瘍内不均一性 / 次世代シークエンサー / がんゲノム / コピーナンバー解析 / circulating tumor DNA / 癌 / 遺伝学 / トランスレーショナルリサーチ / 乳癌 / ctDNA / 次世代シークエンス / 単一癌細胞シークエンス / 単一細胞シークエンス
Outline of Final Research Achievements

I studied at Nick Navin’s Lab at Dep. of Genetics for one year and learned cutting-edge technologies for translational study, such as liquid biopsy and single cell genomic analysis.
We applied novel liquid biopsy technology named PEGASUS to sequence matched blood samples and central system fluid (CSF) from 10 breast cancer patients with leptomeningeal disease. Our data identified aneuploid copy number aberrations and somatic mutations (range: 11-25) in the CSF of 7 patients, including mutations in known driver genes such as BRCA2, TP53 and amplifications of MYC and ERBB2.
Thanks to the great experience there, I continue translational research with the technologies in Japan and keep in touch with great researchers at MDACC.

Academic Significance and Societal Importance of the Research Achievements

帰国後も習得した技術を用いて、乳がん癌性髄膜炎症例におけるCSFと血漿中のctDNAのゲノムプロファイル解析、抗がん剤治療中の腫瘍内不均一性と治療抵抗性に関わる因子を解析するための前向き観察研究、HER2陽性乳がん患者の治療前後のctDNA中のHER2 amplificationの検出について、海外研究者とも連携して研究を継続しており、その成果の一部は国際学会にて発表した。
これらのNext-generation sequencingを基盤とした技術はがんのゲノム研究に関して汎用性が高く、上記以外の課題についても応用することが可能である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (6 results)

All 2019 2018 2017

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] The University of Texas MD Anderson Cancer Center(米国)2017

    • Year and Date
      2017-02-17
    • Related Report
      2018 Annual Research Report
  • [Journal Article] A novel diagnostic method for thyroid follicular tumors based on immunofluorescence analysis of p53-binding protein 1 expression: detection of genomic instability2019

    • Author(s)
      Otsubo Ryota、Matsuda Katsuya、Mussazhanova Zhanna、Sato Ayako、Matsumoto Megumi、Yano Hiroshi、Oikawa Masahiro、Kondo Hisayoshi、Ito Masahiro、Miyauchi Akira、Hirokawa Mitsuyoshi、Nagayasu Takeshi、Nakashima Masahiro
    • Journal Title

      Thyroid

      Volume: 印刷中 Issue: 5 Pages: 657-665

    • DOI

      10.1089/thy.2018.0548

    • NAID

      120006987702

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytogenetic analysis of metaplastic squamous cell carcinoma of the breast inter- and intratumoral heterogeneity.2017

    • Author(s)
      Oikawa M, Igawa A, Taguchi K, Baba K, Ishida M, Akiyoshi S, Yano H, Nagayasu T, Ohno S, Tokunaga E.
    • Journal Title

      Breast Cancer

      Volume: 印刷中 Issue: 6 Pages: 733-741

    • DOI

      10.1007/s12282-017-0768-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Validation of a Novel Diagnostic Kit Using the Semidry Dot-Blot Method to Detect Metastatic Lymph Nodes in Breast Cancer: Distinguishing Macrometastases From Nonmacrometastases.2017

    • Author(s)
      Ryota Otsubo
    • Journal Title

      Clinical breast cancer

      Volume: 17 Issue: 3 Pages: e345-e351

    • DOI

      10.1016/j.clbc.2017.07.009

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Noninvasive genomic profiling of cerebral spinal fluid in breast cancer patient with leptomeningeal disease.2018

    • Author(s)
      Masahiro Oikawa, Naveen Ramesh, Emi Sei, Shanshan Bai, Min Hu, John de Groot, Rashmi K Murthy, Barbara O’Brien, Nicholas E Navin,
    • Organizer
      American Association of Cancer Research (AACR) Annual Meeting 2018.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Noninvasive genomic profiling of cerebral spinal fluid in breast cancer patient with leptomeningeal disease.2018

    • Author(s)
      Masahiro Oikawa, Naveen Ramesh, Emi Sei, Shanshan Bai, Min Hu, John de Groot, Rashmi K Murthy, Barbara O’Brien, Nicholas E Navin
    • Organizer
      American Association of Cancer Research (AACR) Annual Meeting 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-03-15   Modified: 2020-03-30  

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