| Project/Area Number |
15K11288
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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 |
Surgical dentistry
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| Research Institution | Osaka University (2017-2018)
Tokyo Medical and Dental University (2015-2016) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
坂本 啓 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (00302886)
茂櫛 薫 順天堂大学, 医学(系)研究科(研究院), 非常勤講師 (60569292)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 腫瘍内不均一性 / 口腔 / 癌 / ゲノム / 悪性腫瘍 / 不均一性 / 転移 |
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| Outline of Final Research Achievements |
Changes in intratumoral heterogeneity occurring in lymph node metastases in the same patient as tongue cancer primary tumor were analyzed using SNPs array. As a result, CNV was almost identical between the primary lesion and the lymph node metastasis during the metastasis process, but the copy number of the E2F gene increased in a lymph node-specific manner. We found that expression was significantly enhanced in lymph node metastases. In addition, DNA was extracted from FFPE samples of tongue cancer cases with multiple lymph node metastases, and deep sequencing was performed by a next-generation sequencer to identify gene mutations and analyze the frequency of clones having the mutations. As a result, genetic abnormalities were found in TP53, CDKN2A and ATM, and it was found that the frequency of clones having such abnormalities was largely different between primary and lymph node metastasis.
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| Academic Significance and Societal Importance of the Research Achievements |
口腔癌に限らず「腫瘍内不均一性」が、癌治療における大きな障壁になっている。そのため、今後、新規治療法開発に際しては、癌組織という複雑な細胞集団における不均一性の正確な評価が求められる。本研究では口腔癌の「正常→上皮性異形成→浸潤癌」という発癌過程における腫瘍内不均一性の評価法の開発を図り、さらに、リンパ節転移過程における腫瘍内不均一性の解析に初めて取り組み、将来の癌治療への基礎的知見を与えたと考える。
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