| Project/Area Number |
17K16530
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
Takane Kiyoko 東京大学, 医科学研究所, 助教 (60756112)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | 家族性大腸腺腫症 / 大腸癌 / 大腸腺腫 / DNAメチル化 / 腺腫 / KRAS / BRAF / 大腸がん / エピジェネティクス / メチル化 / 大腸線腫 / Lynch症候群 / 家族性大腸ポリポーシス |
|---|
| Outline of Final Research Achievements |
Familial adenomatous polyposis (FAP) is an inherited disorder characterized by numerous colorectal adenomatous polyps with predisposition to the development of colorectal cancer (CRC). Here, we conducted genome-wide DNA methylation analysis of FAP neoplasms. As controls for sporadic colorectal neoplasms and mucosae, we used data from CRC samples, colorectal adenoma samples, normal mucosa samples with reference to public databases. Unsupervised two-way hierarchical clustering analysis of FAP and sporadic CRC/adenoma revealed that CRC was classified into four DNA methylation epigenotypes. FAP neoplasms were classified into at least two molecular subtypes, i.e., normal like methylation type in the majority of cases showing mostly no aberrant methylation and intermediate methylation type in some cases accompanied by KRAS mutations but less frequent aberrant DNA methylation than sporadic neoplasms, suggesting that FAP may follow a tumorigenesis pathway different from that of sporadic CRC.
|
| Academic Significance and Societal Importance of the Research Achievements |
癌症例を詳細にサブタイプ分類し、各症例へ最も良い治療方針を即座に建立するテーラーメード癌治療概念は、癌を克服するための鍵として世界的に研究されている。我々は大腸癌の中でも高リスク群であり早期対応が望まれるにも関わらず疾患の選定や分子機構の解明に乏しかった家族性大腸腺腫症に対して同様の複合的解析を進め、家族性大腸腺腫症の層別化情報を診断や治療へ応用する。日本大腸癌研究会が近年、「遺伝性大腸癌診療ガイドライン」をあえて作成・周知している背景からも、この研究は遺伝性大腸癌の発癌機構解明に大きな寄与をもたらすだけでなく、これまで散発性大腸癌へ誤診されがちであった遺伝性大腸癌患者の救済にも貢献できる。
|
