Epigenetic mechanism of chronic inflammation-associated human carcinogenesis

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790456
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: National Cancer Center Japan
• Principal Investigator: ARAI Eri 独立行政法人国立がん研究センター, 研究所, 研究員 (40446547)
• Project Period (FY): 2011 – 2012
• Keywords: 分子病理 / 腫瘍 / DNA メチル化 / 炎症

Research Abstract

This study has focused on the significance of epigenome alterations in multistage carcinogenesis associated with chronic inflammation. Genome-wide DNA methylation analysis was performed in cancerous and non-cancerous tissue samples obtained from patients with adenocarcinomas of the lung. For comparison, normal lung tissue samples from patients without any primary lung tumor were also analyzed. DNA methylation profiles, which may generate aggressive adenocarcinomas from the inflammatory background in chronic obstructive pulmonary disease in heavy smokers, were identified. Genome-wide DNA methylation analysis also identified DNA methylation profiles each specific to hepatocarcinogenesis associated with hepatitis B virus (HBV) infection and hepatitis C virus infection (HCV) and DNA methylation profiles shared by HBV-positive and HCV-positive patients.

Research Products

• [Journal Article] Prognostic risk stratification of patients with urothelial carcinoma of the bladder with recurrence after radical cystectomy. (2013)
  • Author(s): Nakagawa T, Hara T, Kawahara T, Ogata Y, Nakanishi H, Komiyama M, Arai E, Kanai Y, Fujimoto H
  • Journal Title: J Urol Volume: 189 Pages: 1275-81
  • DOI: DOI:10.1016/j.juro.2012.10.065.
  • Peer Reviewed
• [Journal Article] Ability of preoperative 3.0-Tesla magnetic resonance imaging to predict the absence of side-specific extracapsular extension of prostate cancer. (2013)
  • Author(s): Hara T, Nakanishi H, Nakagawa T, Komiyama M, Kawahara T, Manabe T, Miyake M, Arai E, Kanai Y, Fujimoto H
  • Journal Title: Int J Urol Volume: 29((in print))
  • DOI: DOI:10.1111/iju.12091.
  • Peer Reviewed
• [Journal Article] DNA methylation profiles at precancerous stages associated with recurrence of lung adenocarcinoma. (2013)
  • Author(s): Sato T, Arai E, Kohno T, Tsuta K, Watanabe S, Soejima K, Betsuyaku T, Kanai Y
  • Journal Title: PLoS One Volume: 8 Pages: e59444
  • DOI: DOI:10.1371/journal.pone.0059444
  • Peer Reviewed
• [Journal Article] Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer. (2012)
  • Author(s): Akatsuka S, Yamashita Y, Ohara H, Liu YT, Izumiya M, Abe K, Ochiai M, Jiang L, Nagai H, Okazaki Y, Murakami H, Sekido Y, Arai E, Kanai Y, Hino O, Takahashi T, Nakagama H, Toyokuni S
  • Journal Title: PLoS One Volume: 7 Pages: e43403
  • DOI: DOI:10.1371/journal.pone.0043403
  • Peer Reviewed
• [Journal Article] DNA methyltransferase 3B expression is associated with poor outcome of stage I testicular seminoma. (2012)
  • Author(s): Arai E, Nakagawa T, Wakai-Ushijima S, Fujimoto H, Kanai Y
  • Journal Title: Histopathology Volume: 60 Pages: E12-8
  • DOI: DOI:10.1111/j.1365-2559.2012.04174.x
  • Peer Reviewed
• [Journal Article] Single-CpG-resolution methylome analysis identifies clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas. (2012)
  • Author(s): Arai E, Chiku S, Mori T, Gotoh M, Nakagawa T, Fujimoto H, Kanai Y
  • Journal Title: Carcinogenesis Volume: 33 Pages: 1487-93
  • DOI: DOI:10.1093/carcin/bgs177
  • Peer Reviewed
• [Journal Article] Combined functional genome survey of therapeutic targets for clear cell carcinoma of the kidney. (2011)
  • Author(s): Ito H, Honda K, Satow R, Arai E, Shitashige M, Ono M, Sakuma T, Sakano S, Naito K, Matsuyama H, Yamada T
  • Journal Title: Jpn J Clin Oncol Volume: 41 Pages: 847-53
  • DOI: DOI:10.1093/jjco/hyr060
  • Peer Reviewed
• [Journal Article] and correlation with DNA methylation alterations. (2011)
  • Author(s): Nishiyama N, Arai E, Nagashio R, Fujimoto H, Hosoda F, Shibata T, Tsukamoto T, Yokoi S, Imoto I, Inazawa J, Kanai Y
  • Journal Title: Carcinogenesis Volume: 32 Pages: 462-9
  • DOI: DOI:10.1093/carcin/bgq274
  • Peer Reviewed
• [Journal Article] Diagnosis and prognostication of ductal adenocarcinomas of the pancreas based on genome-wide DNA methylation profiling by bacterial artificial chromosome array-based methylated CpG island amplification. (2011)
  • Author(s): Gotoh M, Arai E, Wakai-Ushijima S, Hiraoka N, Kosuge T, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Kanai Y
  • Journal Title: J Biomed Biotechnol Volume: 2011 Pages: 780836
  • DOI: DOI:10.1155/2011/780836
  • Peer Reviewed
• [Journal Article] Carcinogenetic risk estimation based on quantification of DNA methylation levels in liver tissue at the precancerous stage. (2011)
  • Author(s): Nagashio R, Arai E, Ojima H, Kosuge T, Kondo Y, Kanai Y
  • Journal Title: Int J Cancer Volume: 129 Pages: 1170-9
  • DOI: DOI:10.1002/ijc.26061
  • Peer Reviewed
• [Journal Article] Genome-wide DNA methylation profiles in renal tumors of various histological subtypes and non-tumorous renal tissues. (2011)
  • Author(s): Arai E, Wakai-Ushijima S, Fujimoto H, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, Kanai Y
  • Journal Title: Pathobiology Volume: 78 Pages: 1-9
  • DOI: DOI:10.1159/000322072
  • Peer Reviewed
• [Journal Article] Genetic and epigenetic alterations during renal carcinogenesis. (2011)
  • Author(s): Arai E, Kanai Y
  • Journal Title: Int J Clin Exp Pathol Volume: 4 Pages: 58-73
  • Peer Reviewed
• [Presentation] DNA methylation profiles at precancerous stage cluster lung adenocarcinomas into subclusters associated with carcinogenetic pathway, clinicopathological aggressiveness and patient outcome (2013)
  • Author(s): Sato T, Arai E et al.
  • Organizer: 103rd American Association of Cancer Research Annual Meeting
  • Place of Presentation: Washington D.C., USA
  • Year and Date: 2013-04-10
• [Presentation] Multilayer-omics (whole-exome, methylome and transcriptome) analysis identifies the Wnt/β-catenin pathway as a key player in the development of renal cell carcinoma (2013)
  • Author(s): Arai E et al.
  • Organizer: 103rd American Association of Cancer Research Annual Meeting
  • Place of Presentation: Washington D.C., USA
  • Year and Date: 2013-04-08
• [Presentation] Single-CpG-resolution methylome analysis identifies clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas (2013)
  • Author(s): Arai E et al.
  • Organizer: 9th American Association of Cancer Research-Japanese Cancer Association Joint Conference
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2013-02-23
• [Presentation] DNA methylation profiles at precancerous stage cluster lung adenocarcinomas into subclusters associated with carcinogenetic pathway, clinicopathological aggressiveness and patient outcome (2013)
  • Author(s): Sato T, Arai E et al.
  • Organizer: 9th American Association of Cancer Research-Japanese Cancer Association Joint Conference
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2013-02-23
• [Presentation] 腎淡明細胞がんにおける多層的オミックス(エクソーム・メチローム・トランスクリプトーム)解析 (2012)
  • Author(s): 新井恵吏, 他
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-21
• [Presentation] 前がん段階におけるDNA メチル化異常が肺腺がんの悪性度と予後を規定する (2012)
  • Author(s): 佐藤崇、新井恵吏, 他
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-20
• [Presentation] 尿路上皮がんにおけるゲノム構造異常:臨床病理学的意義ならびにDNA メチル化異常との関係 (2012)
  • Author(s): 西山直隆、新井恵吏, 他
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-20
• [Presentation] ゲノム網羅的DNA メチル化解析による腎淡明細胞がんのCpG アイランドメチル化形質 (2012)
  • Author(s): 新井恵吏, 他
  • Organizer: 日本エピジェネティクス研究会第6回年会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-15
• [Presentation] 肺多段階発がん過程におけるDNA メチル化異常のゲノム網羅的解析 (2012)
  • Author(s): 佐藤崇、新井恵吏, 他
  • Organizer: 日本エピジェネティクス研究会第6回年会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-15
• [Presentation] 肺多段階発がん過程におけるDNA メチル化の変化のゲノム網羅的解析 (2012)
  • Author(s): 佐藤崇、新井恵吏, 他
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-27
• [Presentation] 多層的オミックス解析による疾患の本態解明と臨床応用シンポジウム2「固形がんのエピゲノム解析」 (2012)
  • Author(s): 新井恵吏, 他
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-27
• [Presentation] 腎細胞がん発生過程におけるDNA メチル化異常の網羅的解析 (2011)
  • Author(s): 新井恵吏, 他
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 腎細胞がん発生過程におけるDNA メチル化異常の網羅的解析 (2011)
  • Author(s): 新井恵吏, 他
  • Organizer: 日本エピジェネティクス研究会第5回年会
  • Place of Presentation: 熊本
  • Year and Date: 2011-05-20
• [Presentation] 慢性障害肝におけるDNA メチル化状態を指標とした発がんリスク評価の肝生検検体を用いた臨床応用 (2011)
  • Author(s): 長塩亮、新井恵吏, 他
  • Organizer: 日本エピジェネティクス研究会第5回年会
  • Place of Presentation: 熊本
  • Year and Date: 2011-05-20
• [Presentation] 酸化ストレス誘発ラット腎癌は高度な染色体不安定性を示す (2011)
  • Author(s): 赤塚慎也、新井恵吏, 他
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-04-29
• [Presentation] 泌尿器系腫瘍及びその背景組織のメチル化解析 (2011)
  • Author(s): 新井恵吏, 他
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-04-28
• [Presentation] Copy number alterations in urothelial carcinomas: Their clinicopathological significance and correlation with DNA methylation alterations (2011)
  • Author(s): Nishiyama N, Arai E et al.
  • Organizer: The 102nd Annual Meeting of AACR
  • Place of Presentation: Orlando, USA
  • Year and Date: 2011-04-02
• [Book] DNA methylation alterations in human cancers. In: Epigenetics in Human Disease. (2012)
  • Author(s): Arai E et al.
  • Total Pages: 24
  • Publisher: Elsevier
• [Book] Epigenetics in Human Disease (2011)
  • Author(s): Kanai Y, Arai E.
  • Total Pages: 592
  • Publisher: Academic Press
• [Remarks] ヒト多段階発がん過程におけるエピゲノム異常 : 国立がん研究センター研究所分子病理分野
  • URL: http://www.ncc.go.jp/jp/nccri/divisions/01path/01path01.html