Investigation of genetic alteration and molecular basis of de novo colorectal cancer
Project/Area Number |
26860518
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Gastroenterology
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Research Institution | Yokohama City University |
Principal Investigator |
SAKAI Eiji 横浜市立大学, 医学(系)研究科(研究院), 客員研究員 (30600233)
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 大腸癌 / 遺伝子変異 / 大腸発癌 / DNAメチル化 / de novo癌 / LST |
Outline of Final Research Achievements |
In this study, we revealed molecular basis of laterally spreading tumor (LST), using genome-wide comprehensive analyses. Firstly, we assessed their epigenetic background. Subsequently, we conducted targeted exon sequencing including 38 candidate CRC driver genes. By hierarchical clustering using methylation information, LST was clearly classified into two subtypes; LST-G correlating to IME, and LST-NG correlating to LME. Genes associated with RTK/RAS signaling pathway were mutated more frequently in LST-G than LST-NG (P=0.004), especially KRAS mutation. Both LSTs showed high frequency of APC mutation even at adenoma stage, suggesting its involvement in initiation stage of LST, like adenoma-carcinoma sequence. TP53 mutation was specifically detected in cancer samples. TP53 mutation occurred during development of intramucosal cancer in LST-NG, but during development of cancer with submucosal invasion in LST-G, suggesting involvement of TP53 mutation at earlier stage in LST-NG.
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Report
(3 results)
Research Products
(2 results)