| Project/Area Number |
16K19081
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Human pathology
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| Research Institution | Kobe University |
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Principal Investigator |
FUJIKURA KOHEI 神戸大学, 医学研究科, 特命助教 (50773751)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | IPNB / 遺伝子変異 / 胆管内乳頭状腫瘍 / 胆管癌 / エクソーム解析 / 病理診断 / 予後 / 免疫形質 / 乳頭型胆管癌 |
|---|
| Outline of Final Research Achievements |
Intraductal papillary neoplasms of the bile duct (IPNB) is a biliary tumor which shows predominantly intraductal growth and dilatation of affected ducts, and have a better prognosis. Here we elucidate the genetic landscape of IPNBs. In the whole exome sequencing study, mutations in APC or CTNNB1 were observed in 6/14 subjects (43%) and were mutually exclusive. In immunohistochemistry, the aberrant cytoplasmic and/or nuclear expression of β-catenin was found in not only 5/6 IPNBs with APC or CTNNB1 mutations, but also 6/8 cases with wild-type APC and CTNNB1 (total 79%). Somatic mutations were also identified in genes involved in RAS signalling, a cell cycle regulator, histone methyltransferase, and DNA mismatch repair, some of which are potentially targetable. This study suggests that activation of the Wnt/β-catenin signalling pathway is relevant to the development and progression of IPNBs. IPNBs appeared to be morphologically and genetically distinct from cholangiocarcinomas.
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