| Budget Amount *help |
¥103,740,000 (Direct Cost: ¥79,800,000、Indirect Cost: ¥23,940,000)
Fiscal Year 2014: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2013: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2012: ¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
Fiscal Year 2011: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
Fiscal Year 2010: ¥21,710,000 (Direct Cost: ¥16,700,000、Indirect Cost: ¥5,010,000)
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| Outline of Final Research Achievements |
The purpose of this study was to elucidate the significance of dysregulation of chromatin remodeling and DNA break repair in carcinogenesis; and to propose a therapeutic strategy against cancers with chromatin remodeling dysregulation. Using an originally developed non-homologous end joining assay, a molecular process to start DNA strand break repair; histone acetylation by CBP/p300 leads to accumulation of SWI/SNF chromatin remodeling complex at DNA break sites. Molecular process of RET oncogene fusion driving carcinogenesis, consisting of DNA strand breaks and their illegitimate repair, was also elucidated. Lung cancers without driver oncogene aberrations preferentially showed inactivating mutations and loss/reduced expression of a chromatin remodeling gene, BRG1. BRM-ATPase, a paralog for BRG1, was identified as a therapeutic target by synthetic lethality against BRG-deficient cancer.
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