| Project/Area Number |
16K09309
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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 |
Gastroenterology
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| Research Institution | Kyoto University |
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Principal Investigator |
YAMADA Atsushi 京都大学, 医学研究科, 特定講師 (20569610)
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| Co-Investigator(Kenkyū-buntansha) |
奥野 恭史 京都大学, 医学研究科, 教授 (20283666)
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| Research Collaborator |
KOSUGI Shinji
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| Project Period (FY) |
2016-04-01 – 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 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 大腸がん / Hypermutated-type / “Hypermutated-type” 大腸がん / 「Hypermutated type」大腸癌 / 内科 |
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| Outline of Final Research Achievements |
We analyzed whole exome sequencing data obtained from the Cancer Genome Atlas (TCGA) dataset. Based on microsatellite instability status and mutations in BRAF, POLE and POLD1 genes, we could divide hypermutated-type colon cancer into three subtypes. In addition, these three subtypes had distinct mutational patterns characterized by difference in proportion of single nucleotide substitutions, insertions and deletions.
We next performed immunohistochemical staining for mismatch repair proteins, and found 7.6% of colorectal cancer tissues showed loss of expression of mismatch repair proteins which represent majority of hypermutated-type colorectal cancer. We then analyzed mutational profile by targeted gene sequencing panel, and showed the heterogeneous molecular characteristics among hypermutated-type colorectal cancer stratified by mismatch repair and BRAF V600E mutational status.
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| Academic Significance and Societal Importance of the Research Achievements |
新しいがん治療薬である免疫チェックポイント阻害剤の効果が期待されるタイプのがんとして、“Hypermutated-type”と呼ばれる遺伝子変異が非常に多いタイプのがんが注目されている。今回の研究では“Hypermutated-type”大腸がんを細分類して特徴を検討することにより、それぞれのsubtypeにおける遺伝子変異のパターンが異なるなどの特徴が明らかとなった。この研究成果は大腸がんの病態に対する理解を深める一助となり、さらには個別化医療の確立に役立つことが期待される。
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