2019 Fiscal Year Final Research Report
Identification of molecules involved in genomic damage and their blood monitoring
| Project/Area Number |
16K10514
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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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| Research Field |
Digestive surgery
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| Research Institution | Jichi Medical University |
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Principal Investigator |
SUZUKI Koichi 自治医科大学, 医学部, 准教授 (70332369)
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| Co-Investigator(Kenkyū-buntansha) |
力山 敏樹 自治医科大学, 医学部, 教授 (80343060)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | 染色体不安定性 / Satellite α transcript / セントロメア / ゲノムダメージ / 多発癌 / DNA脱メチル化異常 / 血中モニタリング |
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| Outline of Final Research Achievements |
(1) Induction of chromosomal instability: We constructed lentiviral vectors expressing SAT and then infected human mammary epithelial cells with these vectors. Immunocytochemistry revealed the rates of abnormal segregations of chromosomes, micronuclei and anaphase bridging were significantly higher in the cells with SAT overexpression than in those without. An array CGH identified the specific chromosomes of 8q and 20q as frequent sites of copy number alterations in cells with SAT overexpression (IJO 2018).(2) Field cancerization for the development of multiple cancers: We demonstrated for the first time a strong association between SAT expression levels in normal breast tissues and the development of bilateral breast cancer (BBC),as well as multiple primary cancer (MPC),in other organs when patients with breast cancer lack BRCA related features. These patients exhibited a 22 and 13fold increased risk for the development of BBC and MPC, respectively (Oncology reports 2019).
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| Free Research Field |
腫瘍外科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、SATが介在する染色体不安定性のメカニズムに脱メチル化異常を関連づけて一連のプロセスを検証する独創的な研究課題です。SATが誘導するゲノムダメージの標的分子を特定し、それを血中モニタリングする事で発がんリスクのマーカーとして臨床応用が期待されます。個人のゲノムプロファイルを特定し、その標的分子を簡便かつ低侵襲な方法で経時的に追跡する一連の手法は、発癌リスクの特定のみならず、炎症性疾患や成人病といった複雑な要因からなる様々な疾患にも応用が可能です。リアルタイムに個人の疾患プロファイルの変化を捉え、病気の発症を予測する新たな個別化医療のアプローチです。
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