|Budget Amount *help
¥217,750,000 (Direct Cost: ¥167,500,000、Indirect Cost: ¥50,250,000)
Fiscal Year 2016: ¥32,890,000 (Direct Cost: ¥25,300,000、Indirect Cost: ¥7,590,000)
Fiscal Year 2015: ¥44,070,000 (Direct Cost: ¥33,900,000、Indirect Cost: ¥10,170,000)
Fiscal Year 2014: ¥40,690,000 (Direct Cost: ¥31,300,000、Indirect Cost: ¥9,390,000)
Fiscal Year 2013: ¥49,530,000 (Direct Cost: ¥38,100,000、Indirect Cost: ¥11,430,000)
Fiscal Year 2012: ¥50,570,000 (Direct Cost: ¥38,900,000、Indirect Cost: ¥11,670,000)
|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.