2016 Fiscal Year Research-status Report
胃癌におけるCCND1, CCNE1及びCDK6 遺伝子増幅の検索
| Project/Area Number |
16K08686
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| Research Institution | Kanazawa University |
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Principal Investigator |
大井 章史 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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| Keywords | 胃癌 / サイクリン / サイクリン依存性キナーゼ / 遺伝子増幅 / MLPA / FISH |
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| Outline of Annual Research Achievements |
The aim of the present study was to determine the amplification status of 26 genes, which are frequently amplified in solid cancers, in advanced gastric cancers. A total of 93 formalin-fixed and paraffin-embedded advanced gastric cancer tissues were examined by multiple ligation-dependent probe amplification (MLPA), and 32 cases with ‘gain’ or ‘amplified’ status of 16 genes were further examined for the respective gene amplification by fluorescence in situ hybridization (FISH). The frequencies of gene amplifications in these gastric cancers as assessed by these combined methods were as follows: ERBB2 (14%), FGFR2 (7.5%), MYC (7.5%), TOP2A (7.5%), MET (4.3%), MDM2 (4.3%), CCND1 (3.2%), FGF10 (3.2%), and EGFR (1.1%). Attempts at correlating the FISH status with the immunohistochemical staining pattern showed variable results. In conclusion, combination of MLPA and FISH analysis is a feasible approach for obtaining the semi-comprehensive genetic information that is necessary for personalized molecular targeted therapy.
以上の結果はHuman Pathology (2017) 61: 58-67 に” Gene amplification of CCNE!, CCND1, and CDK6 in gastric cancers detected by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization” に誌上発表した。
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
胃癌におけるCCND1, CCNE1 および CDK6 の遺伝子増幅の検索は順調に進み、ほぼ当初の計画を終了できた。
本研究を遂行中にCCND1とERBB2の同時増幅が高頻度に起こっていることがあきらかになり、さらにCCND1の増幅がERBB2の増幅に先行する可能性が高いことがわかった。乳癌では CCND1の遺伝子座のある 染色体11q11.3 とERBB2の遺伝子座のある17q12-21さらに、11q11と8p11-12の同時増幅が注目されている。胃癌について、これらの3つの領域の遺伝子増幅を解析すべく計画中である。
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| Strategy for Future Research Activity |
胃癌、乳癌について、8p11-12、11q11.3 と17q12-21の増幅をMLPAとFISHを使って解析し、増幅遺伝子を同定し、その意義を解明すると同時に、異なる染色体上の遺伝子が同時増幅するメカニズムを明らかにしたい。
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