| Project/Area Number |
16K20614
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Surgical dentistry
|
|---|
| Research Institution | Tokai University |
|---|
Principal Investigator |
|
|---|
| Research Collaborator |
KIMURA Minoru
KAJIWARA Kagemasa
OTA Yoshihide
HOZUMI Katsuto
TAJIMA Atsushi
HOSOMICHI Kazuyoshi
UCHIBORI Masahiro
OSAWA Yuko
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 口腔がん / NOTCH1 / FAT1 / 口腔扁平上皮癌 / 大規模遺伝子解析 / NOTCH1変異 / NOTCH経路の腫瘍原性 / 遺伝子解析 / 分子生物学的解析 |
|---|
| Outline of Final Research Achievements |
Tumors and oral mucosa tissues were collected at the time of surgical resection from 122 treatment-naive OSCC patients, follow-up from 3.0 years to 8.3. Selected cancer-related genes (502,696 bases, 50 driver genes plus 39 genes which were frequently mutated in previous reports in HNSCC and OSCC in foreign countries) were evaluated.
Results: The average depth of coverage were 168.6× in tumors and 75.5× in normal mucosae. 368 exonic mutations (including 8 splicing and 22 frameshift indels) were observed. The common mutations were found in TP53 (44.6 %), FAT1 (11.6 %), NOTCH1 (11.6 %), USH2A (8.9 %) and PIK3CA (5.4 %), which was similar to data of foreign countries. Progression free survival was significantly longer for patients with FAT1 and NOTCH1-mutated tumors than for those with those of mutation-free tumors (P<0.01). Importantly, 27.8 % of patients have gene mutations in NOTCH pathway, and these mutations were mostly located in the vicinity of NOTCH ligand binding region.
|
| Academic Significance and Societal Importance of the Research Achievements |
口腔がんの遺伝学的情報は解明されていないため、今後の治療戦略に好影響を与えると考えられる。とくに、口腔がんは標準的な化学療法が確立されていないため、手術療法以外の選択肢が増えることが考えられる。また、バイオマーカーの開発により、化学療法の選択的使用など医療経済にも好影響を与えることが予想される。侵襲度の少ない治療の開発は社会経済に好影響を与える可能性まで考えられる。以上より、学術的、社会的に大きな影響を与える可能性のある研究成果である。
|
