2016 Fiscal Year Final Research Report
An integrated genomic analysis on evolution of cancer cell population
| Project/Area Number |
24221011
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical genome science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
TSUTSUMI Shuichi 東京大学, 先端科学技術研究センター, 特任准教授 (30345152)
ISHIKAWA Shumpei 東京医科歯科大学, 難治疾患研究所, 教授 (50418638)
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| Project Period (FY) |
2012-05-31 – 2017-03-31
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| Keywords | ゲノム / エピゲノム / クロマチン / クローン進化 / 微小環境 / 不均一性 / 可塑性 |
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| Outline of Final Research Achievements |
We studied genetic heterogeneity and epigenetic plasticity among the tumor cell population which promote survival and clonal evolution of resistant cell clones and adaptation to the tumor microenvironment.
We demonstrated evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment, which suggest that tumor cells may undergo positive selection during TMZ treatment in the context of mismatch repair deficiency. Adaptation to the intratumoral microenvironment is crucial for tumor cell survival. Under the low pH condition, the transcription factor SREBP2 is activated, leading to tumor cell proliferation by altering acetic acid metabolism with ACSS2 induction.
In summary, epigenomic alteration occurs in various levels, such as chromatin domains, genes, and regulatory regions during tumor development and progression.
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| Free Research Field |
ゲノム科学
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