Pathological Significance of modified nucleic acid base in human tissue.

• Project/Area Number: 24659161
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Human pathology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SUGIMURA Haruhiko 浜松医科大学, 医学部, 教授 (00196742)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: DNA 付加体 / 修飾核酸 / 分子疫学 / etheno DNA adduct / demethylation / TET / TDG / IDH / 塩基修復 / DNA付加体 / DNA修飾 / 発がん / 修復遺伝子 / 胃がん / 人体病理

Research Abstract

Adductomics analysis of alkane substituted exocyclic etheno DNA adducts in human stomach mucosa having gastric cancer was performed for the cases from Lujiang County, Anhui, China, and from Hamamatsu, Japan. Discrimination analysis using quantitative value of 7 lipid per oxidation derived DNA adducts revealed that two regions showed distinctive adductome profile. 3 of 7 DNA adducts in this category were greater in Japanese gastric mucosa than Chinese gastric mucosa, which may suggest gastric carcinogenesis in Japan favor inflammatory or metabolic background. Furthermore, we quantitated 5'-hydroxymethyl deoxycytidine, and its derivatives carboxyl deoxycytidine, and formyl deoxycytidine in gastric cancer and adjacent non-tumor tissues and found the relationship between TET2 expression and 5hmdC. In this attempt we could not identify the adducts specifically high in endemic area of gastric cancer (Lujiang), thus further investigation is necessary.

Research Products

• [Journal Article] YB-1 promotes transcription of cyclin D1 in human non-small-cell lung cancers (2014)
  • Author(s): Harada, M., Kotake, Y., Ohhata, T., Kitagawa, K., Niida, H., Matsuura, S., Funai, K., Sugimura, H., Suda, T. and Kitagawa, M.
  • Journal Title: Genes Cells Volume: 18 Issue: 6 Pages: 999-1006
  • DOI: 10.1111/gtc.12150
  • Peer Reviewed
• [Journal Article] A rare Japanese case with a NUT midline carcinoma in the nasal cavity : A case report with immunohistochemical and genetic analyses (2014)
  • Author(s): Suzuki S, Sugimura H et al.
  • Journal Title: Pathol Res Pract Volume: 210(6) Issue: 6 Pages: 383-8
  • DOI: 10.1016/j.prp.2014.01.013
  • Peer Reviewed
• [Journal Article] An autopsy case of malignant pleural mesothelioma associated with nephrotic syndrome (2014)
  • Author(s): Suzuki S, Sugimura H et al.
  • Journal Title: Intern Med Volume: 53(3) Pages: 243-6
  • NAID: 130003392643
  • Peer Reviewed
• [Journal Article] A novel somatic FGFR3 mutation in primary lung cancer (2014)
  • Author(s): Shinmura K, Sugimura H et al.
  • Journal Title: Oncol Rep Volume: 31(3) Issue: 3 Pages: 1219-24
  • DOI: 10.3892/or.2014.2984
  • Peer Reviewed / Open Access
• [Journal Article] TNK2 gene amplification is a novel predictor of a poor prognosis in patients with gastric cancer (2014)
  • Author(s): Shinmura K, Sugimura H et al.
  • Journal Title: J Surg Oncol Volume: 109(3) Issue: 3 Pages: 189-97
  • DOI: 10.1002/jso.23482
  • Peer Reviewed / Open Access
• [Journal Article] Breakages at YWHAE, FAM22A, and FAM22B loci in uterine angiosarcoma : a case report with immunohistochemical and genetic analysis (2014)
  • Author(s): Suzuki S, Sugimura H et al.
  • Journal Title: Pathol Res Pract Volume: 210(2) Issue: 2 Pages: 130-4
  • DOI: 10.1016/j.prp.2013.09.009
  • Peer Reviewed
• [Journal Article] Sugimura H Establishment and characterization of a mutagenized cell line exhibiting the 'cell-in-cell' phenotype at a high frequency (2013)
  • Author(s): Kahyo T, Sugimura H
  • Journal Title: Genes Cells Volume: 18(11) Issue: 11 Pages: 1042-52
  • DOI: 10.1111/gtc.12092
  • Peer Reviewed
• [Journal Article] SGOL1 variant B induces abnormal mitosis and resistance to taxane in non-small cell lung cancers (2013)
  • Author(s): Matsuura S, Kahyo T, Shinmura K, Iwaizumi M, Yamada H, Funai K, Kobayashi J, Tanahashi M, Niwa H, Ogawa H, Takahashi T, Inui N, Suda T, Chida K, Watanabe Y, *Sugimura H.
  • Journal Title: Sci Rep Volume: 3 Issue: 1 Pages: 3012-3012
  • DOI: 10.1038/srep03012
  • Peer Reviewed / Open Access
• [Journal Article] CD74-ROS1 fusion transcripts in resected non-small cell lung carcinoma (2013)
  • Author(s): Matsuura S, Sugimura H et al.
  • Journal Title: Oncol Rep Volume: 30(4) Issue: 4 Pages: 1675-80
  • DOI: 10.3892/or.2013.2630
  • Peer Reviewed
• [Journal Article] Identification and association study with lung cancer for novel insertion polymorphisms of human endogenous retrovirus. (2013)
  • Author(s): Kahyo T, Sugimura H et al.
  • Journal Title: Carcinogenesis. Volume: 34 Issue: 11 Pages: 2531-8
  • DOI: 10.1093/carcin/bgt253
  • Peer Reviewed
• [Journal Article] Accumulated phosphatidylcholine (16:0/16:1) in human colorectal cancer; possible involvement of LPCAT4. (2013)
  • Author(s): Kurabe N, Hayasaka T, Ogawa M, Masaki N, Yoshimi Ide Y, Waki M, Nakamura T, Kurachi K, Kahyo T, Shinmura K, Midorikawa Y, Sugiyama Y, Setou M, Sugimura H.
  • Journal Title: Cancer Sci Volume: 104 Issue: 10 Pages: 1295-1302
  • DOI: 10.1111/cas.12221
  • Peer Reviewed
• [Journal Article] Early-onset diffuse gastric cancer associated with a de novo large genomic deletion of CDH1 gene (2013)
  • Author(s): Sugimoto S, Sugimura H et al.
  • Journal Title: Gastric Cancer Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] D2-40-positive lymphatic vessel invasion is not a poor prognostic factor in stage I lung adenocarcinoma (2013)
  • Author(s): Shimizu K, Sugimura H et al.
  • Journal Title: Pathol Int Volume: 63(4) Issue: 4 Pages: 201-5
  • DOI: 10.1111/pin.12048
  • Peer Reviewed
• [Journal Article] Visualization of phosphatidylcholine (16:0/16:0) in type II alveolar epithelial cells in the human lung using imaging mass spectrometry. (2013)
  • Author(s): Kurabe N, Sugimura H et al.
  • Journal Title: Pathol Int. Volume: 63 Issue: 4 Pages: 195-200
  • DOI: 10.1111/pin.12050
  • Peer Reviewed
• [Journal Article] Internal frontier: the pathophysiology of the small intestine. (2013)
  • Author(s): Sugimura H and Osawa S
  • Journal Title: World J Gastroenterol. Volume: 19 Issue: 2 Pages: 161-4
  • DOI: 10.3748/wjg.v19.i2.161
  • Peer Reviewed
• [Journal Article] Lipid peroxidation-induced DNA adducts in human gastric mucosa (2012)
  • Author(s): Matsuda T, Tao H, Goto M, Yamada H, Suzuki M, Wu Y, Xiao N, He Q, Guo W, Cai Z, Kurabe N, Ishino K, Matsushima Y, Shinmura K, Konno H, Maekawa M, Wang Y, Sugimura H
  • Journal Title: Carcinogenesis Volume: 34 Issue: 1 Pages: 121-127
  • DOI: 10.1093/carcin/bgs327
  • Peer Reviewed
• [Journal Article] Hepatocellular adenoma associated with familial adenomatous polyposis coli. (2012)
  • Author(s): Inaba K, Sakaguchi T, Kurachi K, Mori H, Tao, H, Nakamura T, Takehara Y, Baba S, Maekawa M, Sugimura H, Konno H
  • Journal Title: World Journal of Hepatology Volume: 4(11) Issue: 11 Pages: 322-326
  • DOI: 10.4254/wjh.v4.i11.322
  • Peer Reviewed
• [Journal Article] Impaired suppressive activities of human MUTYH variant proteins against oxidative mutagenesis (2012)
  • Author(s): Shinmura K, Goto M, Tao H, Matsuura S, Matsuda T, Sugimura H
  • Journal Title: World J Gastroenterol Volume: 18 Issue: 47 Pages: 6935-6942
  • DOI: 10.3748/wjg.v18.i47.6935
  • Peer Reviewed
• [Journal Article] The CRKL gene encoding an adaptor protein is amplified, overexpressed, and a possible therapeutic target in gastric cancer (2012)
  • Author(s): Natsume H, Shinmura K, Tao H, Igarashi H, Suzuki M, Nagura K, Goto M, Yamada H, Maeda M, Konno H, Nakamura S, Sugimura H
  • Journal Title: J Transl Med Volume: 10 Issue: 1 Pages: 97-97
  • DOI: 10.1186/1479-5876-10-97
  • Peer Reviewed
• [Journal Article] Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization (2011)
  • Author(s): Kiyose S, Nagura K, Tao H, Igarashi H, Yamada H, Goto M, Maeda M, Kurabe N, Suzuki M, Tsuboi M, Kahyo T, Shinmura K, Hattori N, Sugimura H
  • Journal Title: Pathol Int Volume: 62 Issue: 7 Pages: 477-484
  • DOI: 10.1111/j.1440-1827.2012.02832.x
  • Peer Reviewed
• [Presentation] The origin of human cancer, a lesson from molecular epidemiology of gastric cancer (2014)
  • Author(s): Haruhiko Sugimura
  • Organizer: 101st Indian Science Congress
  • Place of Presentation: Jammu, India
  • Invited
• [Presentation] Quantitative Analysis of 5-hydroxymethylcytosine in Gastric Cancer by Liquid Chromatography Coupled with Tandem Mass Spectrometry (2013)
  • Author(s): Du CP, Sugimura H
  • Organizer: The 4^<th> JCA-AACR joint conference
  • Place of Presentation: Tokyo bay Maihama Hotel Club Resort, Chiba, Japan
• [Presentation] Germline CDH1 mutations and copy number alterations in hereditary and early onset diffuse gastric cancer (2013)
  • Author(s): Yamada H, Sugimura H et al.
  • Organizer: The 4th JCA-AACR joint conference
  • Place of Presentation: Tokyo bay Maihama Hotel Club Resort, Chiba, Japan
• [Presentation] Towards the genetics and genomics of diffuse gastric cancer (2013)
  • Author(s): Sakamoto H, Sugimura H et al.
  • Organizer: The 4th JCA-AACR joint conference
  • Place of Presentation: Tokyo bay Maihama Hotel Club Resort, Chiba, Japan
• [Presentation] Quantitative Analysis of 5-hydroxymethylcytosine in Gastric Cancer by Liquid Chromatography Coupled with Tandem Mass Spectrometry (2013)
  • Author(s): Du Chunping, Haruhiko Sugimura et al.
  • Organizer: the 4th JCA-AACR Special Joint Conference
  • Place of Presentation: Tokyo Bay Maihama Hotel Club Resort, Chiba, Japan
• [Presentation] Germline CDH1 copy changes in diffuse gastric cancer (2013)
  • Author(s): Yamada H, Sugimura H et al.
  • Organizer: the 4th JCA-AACR Special Joint Conference
  • Place of Presentation: Tokyo Bay Maihama Hotel Club Resort, Chiba, Japan
• [Presentation] Towards the Genetics and Genomics of Diffuse Gastric Cancer (2013)
  • Author(s): Hiromi Sakamoto, Haruhiko Sugimura et al.
  • Organizer: the 4th JCA-AACR Special Joint Conference
  • Place of Presentation: Tokyo Bay Maihama Hotel Club Resort, Chiba, Japan
  • Invited
• [Presentation] DNA Adductome, an ultimate exposome of human tissue. (2012)
  • Author(s): 椙村春彦他
  • Organizer: AACR special conference, post GWAS horizon.
  • Place of Presentation: Hollywood, FL, USA
• [Presentation] The origin of human cancer, a lesson from molecular epidemiology of gastric cancer
  • Author(s): Sugimura H
  • Organizer: The 101^<st> Indian Science Congress
  • Place of Presentation: Jammu, India
• [Presentation] DNA adductome : the most proximal exposome
  • Author(s): Sugimura H et al.
  • Organizer: AACR special conference : Post-GWAS Horizons in Molecular Epidemiology : Digging Deeper into the Environment
  • Place of Presentation: Hollywood, FL, USA
• [Presentation] ヒトアダクトームについて
  • Author(s): 椙村春彦
  • Organizer: 日本分子生物学会
  • Place of Presentation: 福岡市
  • Invited