Diagnostic and therapeutic application of p53 family in esophageal squamous cell carcinoma
Project/Area Number |
17K09354
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Sapporo Medical University |
Principal Investigator |
Sasaki Yasushi 札幌医科大学, 医療人育成センター, 教授 (70322328)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | p53 / p53ファミリー / 食道扁平上皮癌 / NGS / p53 family / p63 / 遺伝子変異 / トランスクリプトーム / 非コードRNA |
Outline of Final Research Achievements |
Genome sequencing studies of cancer have revealed the genomic landscapes of human cancer and have shown that the p53 tumor suppressor gene is most frequently mutated in cancers among the human genes. The p53 family is composed of a group of transcription factors, p53, p73, and p63. A high frequency of p53 mutation has been reported in esophageal squamous cell carcinoma (ESCC). Therefore, loss of p53 function is thought to be very important in ESCC. To identify the direct transcriptional targets of p53 family, we performed RNA sequencing (RNA-seq), chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) analyses and other functional assays. We have isolated several p53 family target transcripts, including protein-coding genes and non-coding RNAs. Our results indicated a p53 family-mediated transcriptional network involved in various biological functions and tumor suppression.
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Academic Significance and Societal Importance of the Research Achievements |
p53はヒト腫瘍において最も高頻度に変異を認めるがん抑制遺伝子である.予後不良な消化器癌である食道扁平上皮癌では70%以上の症例でp53変異が認められるが,変異p53自体は治療標的とはならず,有効な分子標的薬も存在しない.本研究では,食道扁平上皮癌においてp53ネットワーク破綻にともなって変化するトランスクリプトーム(蛋白コード遺伝子,非コードRNA)を網羅的に分析し,個々の関連分子の機能解析を行った.本研究結果は,p53 ネットワークによる腫瘍抑制メカニズムのさらなる理解とそれを標的とした食道扁平上皮癌の治療法開発の基盤形成につながる.
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Report
(5 results)
Research Products
(46 results)
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[Journal Article] Significance of gene mutations in the Wnt signaling pathway in traditional serrated adenomas of the colon and rectum2020
Author(s)
Nakanishi, H. Sawada, T. Kaizaki, Y. Ota, R. Suzuki, H. Yamamoto, E. Aoki, H. Eizuka, M. Hasatani, K. Takahashi, N. Inagaki, S. Ebi, M. Kato, H. Kubota, E. Kataoka, H. Takahashi, S. Tokino, T. Minamoto, T. Sugai, T. Sasaki, Y.
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Journal Title
PLoS One
Volume: 15
Issue: 2
Pages: e0229262-e0229262
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pathogenesis of multiple pancreatic cancers involves multicentric carcinogenesis and intrapancreatic metastasis2020
Author(s)
Fujita, Y. Matsuda, S. Sasaki, Y. Masugi, Y. Kitago, M. Yagi, H. Abe, Y. Shinoda, M. Tokino, T. Sakamoto, M. Kitagawa, Y.
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Journal Title
Cancer Sci
Volume: 111
Issue: 2
Pages: 739-748
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Chemotherapy after progression on nivolumab is essential for responders with genetic alterations of driver gene: Review of two recurrent/metastatic oral squamous cell carcinoma patients2020
Author(s)
Ogi, K. Kobayashi, J. Nakagaki, T. Okamoto, J. Koike, K. Hirokawa, N. Someya, M. Sakamoto, H. Takada, K. Tokino, T. Sasaki, Y. Hiratsuka, H. Miyazaki, A.
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Journal Title
Oral Oncol
Volume: 102
Pages: 104509-104509
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] FGFR Signaling as a Candidate Therapeutic Target for Cancers Resistant to Carbon Ion Radiotherapy2019
Author(s)
Darwis, N. D. M. Nachankar, A. Sasaki, Y. Matsui, T. Noda, S. E. Murata, K. Tamaki, T. Ando, K. Okonogi, N. Shiba, S. Irie, D. Kaminuma, T. Kumazawa, T. Anakura, M. Yamashita, S. Hirakawa, T. Kakoti, S. Hirota, Y. Tokino, T. Iwase, A. Ohno, T. Shibata, A. Oike, T. Nakano, T.
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Journal Title
Int J Mol Sci
Volume: 20
Issue: 18
Pages: 4563-4563
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Malignant paraganglioma of posterior mediastinum; a case report with genetic analysis2019
Author(s)
Adachi Y, Mita H, Sasaki Y, Himori R, Onodera K, Nakamura M, Kikuchi T, Yamashita K, Yukinari Yoshida Y, Ishii Y, Endo T
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Journal Title
Mol Clin Oncol
Volume: 10
Pages: 10-16
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment2018
Author(s)
Wakasugi H, Takahashi H, Niinuma T, Kitajima H, Oikawa R, Matsumoto N, Takeba Y, Otsubo T, Takagi M, Ariizumi Y, Suzuki M, Okuse C, Iwabuchi S, Nakano M, Akutsu N, Kang JH, Matsui T, Yamada N, Sasaki H, Yamamoto E, Kai M, Sasaki Y, Sasaki, Tanaka, Yotsuyanagi, Tsutsumi, Yamamoto, Tokino T , Nakase H, Suzuki H, Itoh F
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Journal Title
Cancer Letters
Volume: 434
Pages: 91-100
DOI
Related Report
Peer Reviewed
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[Journal Article] Prognostic nutritional index and early mortality with percutaneous endoscopic gastrostomy2018
Author(s)
Adachi Y, Akino K, Nojima M, Himori R, Kikuchi T, Mita H, Nakamura M, Tsukuda H, Yamano HO, Sasaki Y, Yoshida Y, Kato Y, Nakase H, Endo T
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Journal Title
QJM
Volume: 111
Issue: 9
Pages: 635-641
DOI
Related Report
Peer Reviewed
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[Journal Article] Assessment of the quality of DNA from various formalin-fixed paraffin-embedded (FFPE) tissues and the use of this DNA for next-generation sequencing (NGS) with no artifactual mutation.2017
Author(s)
Einaga N, Yoshida A, Noda H, Suemitsu M, Nakayama Y, Sakurada A, Kawaji Y, Yamaguchi H, Sasaski Y, Tokino T, Esumi M
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Journal Title
PLoS One
Volume: 12
Issue: 5
Pages: e0176280-e0176280
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Profiling cancer-related gene mutations in oral squamous cell carcinoma from Japanese patients by targeted amplicon sequencing.2017
Author(s)
Nakagaki T, Tamura M, Kobashi K, Koyama R, Fukushima H, Ohashi T, Idogawa M, Ogi K, Hiratsuka H, Tokino T, Sasaki Y
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Journal Title
Oncotarget
Volume: 8
Issue: 35
Pages: 59113-59122
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Patient-specific circulating tumor DNA monitoring using esophageal squamous cell cancer gene panel and digital PCR2019
Author(s)
Iwaya T, Endo F, Sasaki Y, Sasaki N, Yaegashi M, Akiyama Y, Sasaki A, Masuda M, Yamada T, Tokino T, Nishizuka S
Organizer
American Association of Cancer Research (AACR) annual meeting 2019
Related Report
Int'l Joint Research
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