2023 Fiscal Year Final Research Report
Establishment of a minimally invasive, high-throughput method for early diagnosis of malignant mesothelioma
| Project/Area Number |
21K07250
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
米田 和恵 兵庫医科大学, 医学部, 講師 (80724806)
江見 充 兵庫医科大学, 医学部, 特別招聘教授 (90221118)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 悪性中皮腫 / 変異 / ゲノムコピー数解析 |
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| Outline of Final Research Achievements |
Malignant mesothelioma (MM) is an extremely poor prognosis tumor that is refractory to chemotherapy and other treatments. Sequence-level mutations are low at the level of pediatric cancers, and technically elusive microdeletions occur in multiple locations, resulting in genomic reorganization (chromothripsis-like patterns: CTLPs) and frequent biallelic deletions of specific tumor suppressor genes. To capture these changes, we developed a novel method, digital MLPA, to capture mutation patterns associated with MM patient prognosis.
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| Free Research Field |
腫瘍の分子生物学的解析
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| Academic Significance and Societal Importance of the Research Achievements |
次世代シーケンサーによる変異解析が普及しても、捉えるのが難しいのがstructural variants (SVs)であり、MMでは腫瘍が散在、もしくはリンパ球が浸潤したものが多いため腫瘍含有率が低くSV解析が極めて難しい。コピー数変化を伴わないSVは検出できないが、MMで高頻度に生じたエクソンや遺伝子単位の欠失や増幅を網羅的に簡便に捉えるため、新規手法digital MLPA を開発，前処理法も検討することでFFPE切片の解析も可能にした。結果、腫瘍含有率の低い予後良好者の解析が可能となり、予後の良・不良のMM検体間の変異比較を行ったことは、患者予後改善のための基礎データ取得の点で意義深い。
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