Identification of novel drug-responsive cell subpopulations with chromatin accessibility analysis of head and neck cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07383
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: MORI TAISUKE 国立研究開発法人国立がん研究センター, 中央病院, 医員 (00296708)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 頭頸部癌 / ゲノム解析 / 再発・多発 / ヘテロジェネイティ / 治療法開発

Outline of Final Research Achievements

To understand the heterogeneity of head and neck squamous cell carcinoma and the accumulation of genomic aberrations and associated treatment resistance, we analyzed the subpopulations that define diversity together with the mechanisms of tumorigenesis, HPV types, and morphological changes. DNA was extracted from 17 cases, and exome analysis of cancer-related genes was performed. In addition, more than 50 cases of multi-region exome analysis were completed. In addition, we have analyzed recurrent cases including temporal changes and metastatic lymph nodes. This has revealed the presence of at least three clones within a single tumor and potential drug target drivers.

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Free Research Field

分子病理学、人体病理学

Academic Significance and Societal Importance of the Research Achievements

頭頸部癌はアルコールやタバコの要因のみならず、Ｈuman Papiloma VirsやＥpstein-Berr Virus感染,
近年では血液腫瘍に対する骨髄移植後の移植片対宿主病変（Ｇｒａｆｔ　Ｖｅｒｓｕｓ　Ｈｏｓｔ　Ｄisease/GVHD)を起因とした多発、再発がんが問題となっている。これらの疾患の本質は、フィールドキャンサライぜーションと呼称される領域全体のゲノム変異の蓄積である。ほん研究の成果はそれらの領域的なヘテロジェネイティを理解すること、腫瘍の薬剤耐性のメカニズムを理解し、治療方針や予防、再発のリスク評価などの患者のフォローアップ方法のエビデンスを確立することにある。