Integrative genomics and epigenomics for personalized cancer medicine
Project/Area Number |
17015012
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Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
INAZAWA Johji Tokyo Medical and Dental University, 難治疾患研究所, 教授 (30193551)
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Co-Investigator(Kenkyū-buntansha) |
IMOTO Issei 東京医科歯科大学, 難治疾患研究所, 教授 (30258610)
KOZAKI Kenichi 東京医科歯科大学, 硬組織疾患ゲノムセンター, 特任准教授 (50270715)
横井 左奈 東京医科歯科大学, 難治疾患研究所, 助手 (30372452)
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Project Period (FY) |
2005 – 2009
|
Project Status |
Completed (Fiscal Year 2009)
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Budget Amount *help |
¥116,500,000 (Direct Cost: ¥116,500,000)
Fiscal Year 2009: ¥23,200,000 (Direct Cost: ¥23,200,000)
Fiscal Year 2008: ¥23,400,000 (Direct Cost: ¥23,400,000)
Fiscal Year 2007: ¥23,400,000 (Direct Cost: ¥23,400,000)
Fiscal Year 2006: ¥23,400,000 (Direct Cost: ¥23,400,000)
Fiscal Year 2005: ¥23,100,000 (Direct Cost: ¥23,100,000)
|
Keywords | がん / ゲノム / エピゲノム / マイクロアレイ / がん遺伝子 / がん抑制遺伝子 / マイクロRNA / CGH / 個性診断 / 分子標的治療 / CGHアレイ / DNAメチル化 / GhIP法 / BAMCA法 / アレイCGH / ChIP法 |
Research Abstract |
Innovative techniques for detection of genomic and epigenomic aberrations underlying the pathogenesis have been developed and using those techniques numerous cancer-related genes have been successfully identified during the course of the research program. In particular, we identified 10 candidate oncogenes including DUSP26 and SMYD2 up-regulated due to gene amplification, and 10 candidate tumor suppressor genes including DBC1 and PCDH17. Furthermore four tumor-suppressor microRNAs, miR-13 and miR-193a, or miR-124 and miR-203, epigenetically silenced, were successfully identified in oral cancer or hepatocellular carcinoma, respectively.
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Report
(6 results)
Research Products
(551 results)
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[Journal Article] Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous-cell carcinoma.2010
Author(s)
Haruki S, Imoto I, Kozaki K, Matsui T, Kawachi H, Komatsu S, Muramatsu T, Shimada Y, Kawano T, Inazawa J
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Journal Title
Carcinogenesis. 31
Pages: 1027-36
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[Journal Article] Gene-expression phenotypes for vascular invasiveness of hepatocellular carcinomas.2009
Author(s)
Tanaka S, Mogushi K, Yasen M, Noguchi N, Kudo A, Nakamura N, Ito K, Miki Y, Inazawa J, Tanaka H, Arii S
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Journal Title
Surgery. 147
Pages: 405-14
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[Journal Article] Genome-wide DNA methylation profiles in urothelial carcinomas and urothelia at the precancerous stage.2009
Author(s)
Nishiyama N, Arai E, Chihara Y, Fujimoto H, Hosoda F, Shibata T, Kondo T, Tsukamoto T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, Kanai Y
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Journal Title
Cancer Sci. 101
Pages: 231-40
NAID
Related Report
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[Journal Article] Resequencing and copy number analysis of the human tyrosine kinase gene family in poorly differentiated gastric cancer.2009
Author(s)
Kubo T, Kuroda Y, Shimizu H, Kokubo A, Okada N, Hosoda F, Arai Y, Nakamura Y, Taniguchi H, Yanagihara K, Imoto I, Inazawa J, Hirohashi S, Shibata T
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Journal Title
Carcinogenesis. 30
Pages: 1857-64
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[Journal Article]2009
Author(s)
Nakamura Y, Migita T, Hosoda F, Okada N, Gotoh M, Arai Y, Fukushima M, Ohki M, Miyata S, Takeuchi K, Imoto I, Katai H, Yamaguchi T, Inazawa J, Hirohashi S, Ishikawa Y, Shibata T
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Journal Title
Int J Cancer. 125
Pages: 1859-67
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[Journal Article] Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma.2009
Author(s)
Arai E, Ushijima S, Gotoh M, Ojima H, Kosuge T, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, Kanai Y
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Journal Title
Int J Cancer. 125
Pages: 2854-62
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[Journal Article] Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous-cell carcinoma.2009
Author(s)
Komatsu S, Imoto I, Tsuda H, Kozaki K, Muramatsu T, Shimada Y, Aiko S, Yoshizumi Y, Ichikawa D, Otsuji E, Inazawa J
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Journal Title
Carcinogenesis. 30
Pages: 1139-46
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[Journal Article] ASK1 amd ASK2 differentially regulate the counteracting roles of apoptosis and inflammation in tumorigenesis.2009
Author(s)
Iriyama T, Takeda K, Nakamura H, Motimoto Y, Kuroiwa T, Mizukami J, Umeda T, Noguchi T, Naguro I, Nishitoh H, Saegusa K, Tobiume K, Homma T, Shimada Y, Tsuda H, Aiko S, Imoto I, Inazawa J, Chiba K, Kamei Y, Kozuma S, Taketani Y, Matsuzawa A, Ichijo H
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Journal Title
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[Journal Article] PH domain-only protein PHLDA3 is a p53-regulated repressor of Akt.2009
Author(s)
Kawase T, Ohki R, Shibata T, Tsutsumi S, Kamimura N, Inazawa J, Ohta T, Ichikawa H, Aburatani H, Tashiro F, Taya Y
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Journal Title
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[Journal Article] SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells.2009
Author(s)
Takahata M, Inoue Y, Tsuda H, Imoto I, Koinuma D, Hayashi M, Ichikura T, Yamori T, Nagasaki K, Yoshida M, Matsuoka M, Morishita K, Yuki K, Hanyu A, Miyazawa K, Inazawa J, Miyazono K, Imamura T:
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Journal Title
J Biol Chem. 284
Pages: 3334-44
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[Journal Article] Genome-wide DNA methylation profiles in both precancerous conditions and clear cell renal cell carcinomas are correlated with malignant potential and patient outcome.2009
Author(s)
Arai E, Ushijima S, Fujimoto H, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, Kanai Y
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Journal Title
Carcinogenesis. 30
Pages: 214-21
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[Journal Article] Genetic clustering of clear cell renal cell carcinoma based on array-comparative genomic hybridization: its association with DNA methylation alteration and patient outcome.2008
Author(s)
Arai E, Ushijima S, Tsuda H, Fujimoto H, Hosoda F, Shibata T, Kondo T, Imoto I, Inazawa J, Hirohashi S, Kanai Y
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Journal Title
Clin Cancer Res. 14
Pages: 5531-9
Related Report
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[Journal Article] Expression and gene amplification of actinin-4 in invasive ductal carcinoma of the pancreas.2008
Author(s)
Kikuchi S, Honda K, Tsuda H, Hiraoka N, Imoto I, Kosuge T, Umaki T, Onozato K, Shitashige M, Yamaguchi U, Ono M, Tsuchida A, Aoki T, Inazawa J, Hirohashi S, Yamada T
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Journal Title
Clin Cancer Res. 14
Pages: 5348-56
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[Journal Article] Activation of B-Myb by E2F1 in hepatocellular carcinoma.2008
Author(s)
Nakajima T, Yasui K, Zen K, Inagaki Y, Fujii H, Minami M, Tanaka S, Taniwaki M, Itoh Y, Arii S, Inazawa J, Okanoue T:
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Journal Title
Hepatol Res. 38
Pages: 886-95
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[Journal Article] Frequent inactivation of a putative conditional tumor-suppressor gene, angiopoietin-like protein 2, in ovarian cancer.2008
Author(s)
Kikuchi R, Tsuda H, Kozaki K, Kanai Y, Kasamatsu T, Sengoku K, Hirohashi S, Inazawa J, Imoto I
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Journal Title
Cancer Res. 68
Pages: 5067-75
Related Report
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[Journal Article] Frequent silencing of a putative tumor suppressor gene melatonin receptor 1A (MTNR1A) in oral squamous-cell carcinoma.2008
Author(s)
Nakamura E, Kozaki K, Tsuda H, Suzuki, E, Pimkhaokham A, Yamamoto G, Irie T, Tachikawa T, Amagasa T, Inazawa J, Imoto I
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Journal Title
Cancer Sci. 99
Pages: 1390-400
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[Journal Article] Aurora kinase B is a predictive factor for the aggressive recurrence of hepatocellular carcinoma after curative hepatectomy.2008
Author(s)
Tanaka S, Arii S, Yasen M, Moqushi K, Su NT, Zhao C, Imoto I, Eishi Y, Inazawa J, Miki Y, Tanaka H
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Journal Title
Br J Surg. 95
Pages: 611-619
Related Report
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[Journal Article] Overexpressed NF-{kappa}B inducing kinase contributes to the tumorigenesis of adult T-cell leukemia and Hodgkin Reed-Sternberg cells.2008
Author(s)
Saitoh Y, Yamamoto N, Dewan MZ, Sugimoto H, Martinez BVJ, Iwasaki Y, Matsubara K, Qi X, Saitoh T, Imoto I, Inazawa J, Utsunomiya A, Watanabe T, Masuda T, Yamamoto N, Yamaoka S
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Journal Title
Blood. 111
Pages: 5118-29
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[Journal Article] Genetically distinct and clinically relevant classification of hepatocellular carcinoma: putative therapeutic targets.2007
Author(s)
Katoh H, Ojima H, Kokubu A, Saito S, Kondo T, Kosuge T, Hosoda F, Imoto I, Inazawa J, Hirohashi S, Shibata T
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Journal Title
Gastroenterology. 133
Pages: 1475-86
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[Journal Article] Redefining the disease locus of 16q22. 1-linked autosomal dominant cerebellar ataxia.2007
Author(s)
Amino T, Ishikawa K, Toru S, Ishiguro T, Sato N, Tsunemi T, Murata M, Kobayashi K, Inazawa J, Toda T, Mizusawa H
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Journal Title
J Hum Genet. 52
Pages: 643-9
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[Journal Article] Genetic analysis of multifocal superficial urothelial cancers by array-based comparative genomic hybridisation.2007
Author(s)
Kawanishi H, Takahashi T, Ito M, Matsui Y, Watanabe J, Ito N, Kamoto T, Kadowaki T, Tsujimoto G, Imoto I, Inazawa J, Nishiyama H, Ogawa O
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Journal Title
Br J Cancer. 97
Pages: 260-6
Related Report
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[Journal Article] Partial tandem duplication of GRIA3 in a male with mental retardation.2007
Author(s)
Chiyonobu T, Hayashi S, Kobayashi K, Morimoto M, Miyanomae Y, Nishimura A, Nishimoto A, Ito C, Imoto I, Sugimoto T, Jia Z, Inazawa J, Toda T
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Journal Title
Am J Med Genet A. 143
Pages: 1448-5
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[Journal Article] Frequent methylation-associated silencing of a candidate tumor-suppressor, CRABP1, in esophageal squamous-cell carcinoma.2007
Author(s)
Tanaka K, Imoto I, Inoue J, Kozaki K, Tsuda H, Shimada Y, Aiko S, Yoshizumi Y, Iwai T, Kawano T, Inazawa J
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Journal Title
Oncogene. 26
Pages: 6456-68
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[Journal Article] Genome-wide array-based comparative genomic hybridization analysis of pancreatic adenocarcinoma: identification of genetic indicators that predict patient outcome.2007
Author(s)
Loukopoulos P, Shibata T, Katoh H, Kokubu A, Sakamoto M, Yamazaki K, Kosuge T, Kanai Y, Hosoda F, Imoto I, Ohki M, Inazawa J, Hirohashi S
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Journal Title
Cancer Sci. 98
Pages: 392-400
Related Report
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[Journal Article] Reduced levels of ATF-2 predispose mice to mammary tumors.2007
Author(s)
Maekawa T, Shinagawa T, Sano Y, Sakuma T, Nomura S, Nagasaki K, Miki Y, Saito-Ohara F, Inazawa J, Kohno T, Yokota J, Ishii S
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Journal Title
Mol Cell Biol 27
Pages: 1730-44
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[Journal Article] The selective continued linkage of centromeres from mitosis to interphase in the absence of mammalian separase.2006
Author(s)
Kumada K, Yao R, Kawaguchi T, Karasawa M, Hoshikawa Y, Ichikawa K, Sugitani Y, Imoto I, Inazawa J, Sugawara M, Yanagida M, Noda T
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Journal Title
J Cell Biol 172
Pages: 835-46
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[Journal Article] ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation.2005
Author(s)
Takada H, Imoto I, Tsuda H, Nakanishi Y, Ichikura T, Mochizuki H, Mitsufuji S, Hosoda F, Hirohashi S, Ohki M, Inazawa J
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Journal Title
Oncogene. 24
Pages: 8051-60
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[Journal Article] Array-based comparative genomic hybridization analysis of high-grade neuroendocrine tumors of the lung.2005
Author(s)
Peng WX, Shibata T, Katoh H, Kokubu A, Matsuno Y, Asamura H, Tsuchiya R, Kanai Y, Hosoda F, Sakiyama T, Ohki M, Imoto I, Inazawa J, Hirohashi S
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Journal Title
Cancer Sci. 96
Pages: 661-7
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[Journal Article] Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization: Identification of genetic indicators to predict patient outcome.2005
Author(s)
Katoh H, Shibata T, Kokubo A, Ojima H, Loukopoulos P, Kanai Y, Kosuge T, Fukayama M, Kondo T, Sakamoto M, Hosoda F, Ohki M, Imoto I, Inazawa J, Hirohashi S
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Journal Title
J Hepatol. 43
Pages: 863-74
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[Journal Article] Genetic classification of lung adenocarcinoma based on array-based comparative genomic hybridization analysis: its association with clinicopathologic features.2005
Author(s)
Shibata T, Uryu S, Kokubu A, Hosoda F, Ohki M, Sakiyama T, Matsuno Y, Tsuchiya R, Kanai Y, Kondo T, Imoto I, Inazawa J, Hirohashi S
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Journal Title
Clin Cancer Res. 11
Pages: 6177-85
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[Journal Article] Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine.2005
Author(s)
Matsumoto T, Okamoto R, Yajima T, Mori T, Okamoto S, Ikeda Y, Mukai M, Yamazaki M, Oshima S, Tsuchiya K, Nakamura T, Kanai T, Okano H, Inazawa J, Hibi T, Watanabe M
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Journal Title
Gastroenterology. 128
Pages: 1851-67
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[Journal Article] Diagnostic clinical application of two-color fluorescence in situ hybridization that detects chromosome 1 and 17 alterations to direct touch smear and liquid-based thin-layer cytologic preparations of endometrial cancers.2005
Author(s)
Susumu N, Aoki D, Noda T, Nagashima Y, Hirao T, Tamada Y, Banno K, Suzuki A, Tsuda H, Inazawa J, Nozawa S
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Journal Title
Int J Gynecol Cancer. 15
Pages: 70-80
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[Journal Article] Correlation of KIT and EGFR overexpression with invasive ductal breast carcinoma of the solid-tubular subtype, nuclear grade 3, and mesenchymal or myoepithelial differentiation.2005
Author(s)
Tsuda H, Morita D, Kimura M, Shinto E, Ohtsuka Y, Matsubara O, Inazawa J, Takami K, Mochizuki H, Tamai S, Hiraide H
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Journal Title
Cancer Sci. 96
Pages: 48-53
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[Journal Article] DEK oncoprotein regulates transcriptional modifiers and sustains tumor initiation activity in high-grade neuroendocrine carcinoma of the lung.
Author(s)
Shibata T, Kokubu A, Miyamoto M, Hosoda F, Gotoh M, Tsuta K, Asamura H, Matsuno Y, Kondo T, Imoto I, Inazawa J, Hirohashi S
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[Presentation]2008
Author(s)
Inazawa J
Organizer
The 4th Asia Pacific Medical Education Initiative on Molecular Targeted Therapy of Cancer (MTTC).
Place of Presentation
Westin Hotel Tokyo, Tokyo-Japan.
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[Presentation] Epigenetic silencing of TSOC25 by hypermethylation of the CpG island in oral cancer.2007
Author(s)
Nakamura E, Suzuki E, Nakagawa T, Tsuda H, Yamamoto G, Kozaki K, Irie T, Tachikawa T, Amagasa T, Imoto I, Inazawa J
Organizer
98th annual meeting of American Association for Cancer Research 2007
Place of Presentation
LosAngeles, USA
Year and Date
2007-04-16
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[Presentation] Frequent silencing of the candidate tumor-suppressor PCDH20 by epigenetic mechanism in non-small cell lung cancers.2006
Author(s)
Takada T, Tanaka K, Inoue J, Yokoi S, Hosoda H, Shibata T, Sunamori M, Hosoda F, Ohki M, Hirohashi S, Inazawa J
Organizer
97th annual meeting of American Association for Cancer Research 2006
Place of Presentation
Washington D.C. USA
Year and Date
2006-04-04
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[Presentation] Frequent Silencing of the Candidate Tumor-suppressor PCDH20 by Epigenetic Mechanism in Non-Small Cell Lung Cancers.2006
Author(s)
Imoto I, Izumi H, Takada H, Tanaka K, Inoue J, Yokoi S, Hosoda H, Shibata T, Sunamori M, Hosoda F, Ohki M, Hirohashi S, Inazawa J
Organizer
97th annual meeting of American Association for Cancer Research 2006
Place of Presentation
Washington D.C. USA
Year and Date
2006-04-02
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[Presentation] Methylation-associated silencing of a candidate tumor suppression gene, TSEC1, in esophageal squamous-cell carcinoma, identified by bacterial artificial chromosome array-based methylated CpG island amplification (BAMCA).2006
Author(s)
Tanaka K, Imoto I, Inoue J, Tsuda H, Suzuki E, Shimada Y, Kawano T, Iwai T, Inazawa J:
Organizer
97th annual meeting of American Association for Cancer Research 2006
Place of Presentation
Washington D.C. USA
Year and Date
2006-04-02
Related Report
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[Presentation] ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation.2005
Author(s)
Imoto I, Takada H, Tsuda H, Nakanishi Y, Ichikura T, Mochizuki H, Hosoda F, Hirohashi S, Ohki M, Inazawa J
Organizer
The American Society of Human Genetics 55th Annual Meeting
Place of Presentation
Salt Lake City, Utah
Year and Date
2005-10-28
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[Book] 講義録腫瘍学2009
Author(s)
稲澤譲治, 他
Total Pages
240
Publisher
株式会社メジカルビュー社
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[Book] 細胞工学2007
Author(s)
井本逸勢、稲澤譲治
Total Pages
90
Publisher
株式会社秀潤社
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[Book] ゲノム医学2006
Author(s)
小崎健一, 稲澤譲治
Total Pages
113
Publisher
メディカルレビュー社
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