Chromosomal instability induced by DNA demethylation alterations
| Project/Area Number |
25462035
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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 |
Digestive surgery
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| Research Institution | Jichi Medical University |
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Principal Investigator |
Suzuki Koichi 自治医科大学, 医学部, 講師 (70332369)
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| Co-Investigator(Kenkyū-buntansha) |
RIKIYAMA Toshiki 自治医科大学, 医学部, 教授 (80343060)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | Satelliteα / 遺伝子修飾異常 / non-cording RNA / セントロメア / 染色体不安定性 / 染色体分配 / 加齢 / ゲノム損傷 / 脱メチル化異常 / Satelliteαtranscript / DNA脱メチル化異 / satellite alpha |
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| Outline of Final Research Achievements |
Impairment of stability in chromosomal structure facilitates abnormal segregation of chromosome, increasing the risk of carcinogenesis. Segregation is managed by appropriate methylation, leading to heterochromatin structure at centromere. Insufficient methylation such as demethylation fails to heterochromatin due to overexpression of satellite alpha transcript (SatA), which is the non-coding RNA transcribed from satellite alpha sequences at centromere. We showed SatA expression was increased in colorectal cancer, in which satellite sequences were demethylated, resulting in chromosomal instability. We verified this machinery in vitro. The lentiviral vector expressing human SatA was constructed and transduced in cultured cells. Copy number alterations were observed at several chromosomes in transduced cells but not in mock cells. Alterations were frequently seen at chromosome 8q and 20q, which is consistent with the results in clinical specimens.
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Report
(3 results)
Research Products
(11 results)
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[Presentation] Liquid biopsy leads to a paradigm shift in cancer treatment.2016
Author(s)
Koichi Suzuki, Yuji Takayama, Tsutomu Daito, Kosuke Ichida, Taro Fukui, Yuta Muto, Nao Kakizawa, Yuji Kaneda, Fumiaki Watanabe, Fumi Hasegawa, Masaaki Saito, Shingo Tsujinaka, Kazushige Futsuhara, Yasuyuki Miyakura, Hiroshi Noda, Hirokazu Kiyozaki, Fumio Konishi, Toshiki Rikiyama
Organizer
Gastrointestinal Cancers Symposium
Place of Presentation
San Francisico
Year and Date
2016-01-21
Related Report
Int'l Joint Research
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[Presentation] Detection of satellite alpha transcript in sera, as a surrogate marker for the risk of development of multiple cancers in colorectal cancer patients.2015
Author(s)
Kosuke Ichida, Koichi Suzuki, Yuji Takayama, Yuta Muto, Taro Fukui, Takaharu Kato, Masaaki Saito, Fumiaki Watanabe, Nao Kakizawa, Hirofumi Imoto, Hiroyuki Tanaka, Yuji Kaneda, Yusuke Taniyama, Shingo Tsujinaka, Osamu Takata, Yasuyuki Miyakura, Hiroshi Noda, Hirokazu Kiyozaki, Fumio Konishi, Toshiki Rikiyama
Organizer
American Society of Clinical Oncology
Place of Presentation
chicago
Year and Date
2015-05-29
Related Report
Int'l Joint Research
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[Presentation] Emergence of KRAS mutation in detection of circulating tumor DNA during treatments for metastatic gastrointestinal cancer patients.2015
Author(s)
Yuji Takayama, Koichi Suzuki, Tsutomu Daito, Kosuke Ichida, Taro Fukui, Yuta Muto, Nao Kakizawa, Hirofumi Imoto, Yusuke Taniyama, Yuji Kaneda, Hiroyuki Tanaka, Fumiaki Watanabe, Takaharu Kato, Fumi Hasegawa, Masaaki Saito, Shingo Tsujinaka, Yasuyuki Miyakura, Hiroshi Noda, Fumio Konishi, Toshiki Rikiyama
Organizer
American Society of Clinical Oncology
Place of Presentation
chicago
Year and Date
2015-05-29
Related Report
Int'l Joint Research
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