Analysis of gene amplifications of CCND1, CCNE1, and CDK6 in gastric cancers.
| Project/Area Number |
16K08686
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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 |
Human pathology
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| Research Institution | Kanazawa University |
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Principal Investigator |
Ooi Akishi 金沢大学, 医学系, 教授 (50160411)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 胃癌 / 乳癌 / 遺伝子増幅 / MLPA / FISH / gene amplification / breast cancer / サイクリン / サイクリン依存性キナーゼ |
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| Outline of Final Research Achievements |
In solid cancers amplified genes are potential targets of molecular therapies. In this study the 16 genes and 22 genes reportedly amplified in gastric and mammary cancers were examined by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization. In gastric cancers amplification of G1-S regulatory genes (CCNE1, CCND1and CDK6) were co-amplified with ERBB2, EGFR and/or KRAS in single cancer nuclei. In breast cancers The frequencies of the amplification of four regions containing known driver oncogenes were as follows: 8p11 (ZNF703, FGFR1, ADAM9 and IKBKB), 8q24 (MYC), 11q13 (CCND1, C11ORF30), and 17q11-21 (CPD, MED1, ERBB2, CDC6, TOP2A, MAPT) exhibited amplification in 9.6%, 9.6%, 12.4%, and 12.1% of the tumors, respectively. Co-localization of the amplicon on 8p11 and the amplicon on 11q13 in single cells was frequently observed. Precise and feasible analysis of gene amplification status can be obtained using a combination of MLPA and FISH.
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| Academic Significance and Societal Importance of the Research Achievements |
固形癌において増幅遺伝子はしばしば分子標的の対象となる。本研究では胃癌、乳癌において標的候補遺伝子の出現頻度と分布を明らかし、創薬開発に貢献できた。また、分子標的療法を考えるとき、複数の遺伝子増幅が単一腫瘍細胞でおこっていることを念頭に入れることを喚起した。さらに、multiplex ligation-dependent probe amplificartion は比較的安価で網羅的に遺伝子増幅を知る手段であること、一方、fluorescence in situ hybridization は組織切片に適用することによって癌の’進化’の過程を終える手段であることを証明できた。
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Report
(4 results)
Research Products
(7 results)
