Identification of biological characterization and predictive factors for therapeutic effect in primary diffuse large B-cell lymphoma of the central nervous system

• Project/Area Number: 24790341
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Hokkaido University
• Principal Investigator: KANAKO Hatanaka 北海道大学, 大学病院, 助教 (10399834)
• Co-Investigator(Renkei-kenkyūsha): MATSUNO Yoshihiro 北海道大学, 北海道大学病院, 教授 (00199829) ; HATANAKA Yutaka 北海道大学, 北海道大学病院, 特任講師 (30589924) ; KOBAYASHI Hiroyuki 北海道大学, 大学院医学研究科, 講師 (70374478)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 中枢神経 / 悪性リンパ腫 / 中枢神経原発悪性リンパ腫 / 治療効果予測

Outline of Final Research Achievements

In this study, we investigated the methylation status of MGMT, CDKN2A, DAPK1 and LINE1 promoters, and the association with clinicopathological features, response to treatment and clinical outcome in primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) treated with high-dose methotrexate plus radiation therapy (HD-MTX + RT). Pyrosequencing was used to determine methylation rate of these genes, and statistical analysis was performed in groups dichotomized by median of these rates. We demonstrated that 1) LINE1 and DAPK1 hypomethylation could be useful predictors of favorable survival in patients with PCNS-DLBCL treated with HD-MTX+RT. 2) CDKN2A and DAPK1 hypomethylation may predict clinical response to HD-MTX treatment prior to RT, while there was no association between response to the treatment and methylation status of LINE1 and MGMT.

Research Products

• [Journal Article] Immunohistochemical Validation and Expression Profiling of NKG2D Ligands in a Wide Spectrum of Human Epithelial Neoplasms. (2015)
  • Author(s): Fujita H, Hatanaka Y, Sutoh Y, Suzuki Y, Oba K, Hatanaka KC, Mitsuhashi T, Otsuka N, Fugo K, Kasahara M, Matsuno Y.
  • Journal Title: J Histochem Cytochem. Volume: 63 Issue: 3 Pages: 217-227
  • DOI: 10.1369/0022155414563800
  • Peer Reviewed / Open Access
• [Journal Article] Allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning for mycosis fungoides and Sezary syndrome. (2014)
  • Author(s): Shiratori S, Fujimoto K, Nishimura M, Hatanaka KC, Kosugi-Kanaya M, Okada K, Sugita J, Shigematsu A, Hashimoto D, Endo T, Kondo T, Abe R, Hashino S, Matsuno Y, Shimizu H, Teshima T.
  • Journal Title: Hematol Oncol Volume: Epub Ahead of Print Issue: 1 Pages: 9-16
  • DOI: 10.1002/hon.2162
  • NAID: 120005981361
  • Peer Reviewed / Open Access
• [Journal Article] Usefulness of 11C-methionine-positron emission tomography for the diagnosis of progressive multifocal leukoencephalopathy. (2014)
  • Author(s): Shirai S, Yabe I, Kano T, Shimizu Y, Sasamori T, Sato K, Hirotani M, Nonaka T, Takahashi I, Matsushima M, Minami N, Nakamichi K, Saijo M, Hatanaka KC, Shiga T, Tanaka S, Sasaki H.
  • Journal Title: J Neurol Volume: 261 Issue: 12 Pages: 2314-2318
  • DOI: 10.1007/s00415-014-7500-y
  • Peer Reviewed
• [Journal Article] Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer. (2014)
  • Author(s): Hosoda M, Yamamoto M, Nakano K, Hatanaka KC, Takakuwa E, Hatanaka Y, Matsuno Y, Yamashita H
  • Journal Title: Breast Cancer Res Treat. Volume: 144 Issue: 2 Pages: 249-61
  • DOI: 10.1007/s10549-014-2867-0
  • NAID: 120005600744
  • Peer Reviewed
• [Journal Article] p53 accumulation is a strong predictor of recurrence in estrogen receptor-positive breast cancer patients treated with aromatase inhibitors. (2014)
  • Author(s): Yamamoto M, Hosoda M, Nakano K, Jia S, Hatanaka KC, Takakuwa E, Hatanaka Y, Matsuno Y, Yamashita H
  • Journal Title: Cancer Sci Volume: 105 Issue: 1 Pages: 81-8
  • DOI: 10.1111/cas.12302
  • NAID: 120005411143
  • Peer Reviewed
• [Journal Article] Co-overexpression of GEP100 and AMAP1 proteins correlates with rapid local recurrence after breast conservative therapy. (2013)
  • Author(s): Kinoshita R, Nam JM, Ito YM, Hatanaka KC, Hashimoto A, Handa H, Otsuka Y, Hashimoto S, Onodera Y, Hosoda M, Onodera S, Shimizu S, Tanaka S, Shirato H, Tanino M, Sabe H.
  • Journal Title: PLoS One. Volume: 8 Issue: 10 Pages: e76791-e76791
  • DOI: 10.1371/journal.pone.0076791
  • NAID: 120005348196
  • Peer Reviewed
• [Journal Article] β1-integrin via NF-κB signaling is essential for acquisition of invasiveness in a model of radiation treated in situ breast cancer. (2013)
  • Author(s): Nam JM, Ahmed KM, Costes S, Zhang H, Onodera Y, Olshen AB, Hatanaka KC, Kinoshita R, Ishikawa M, Sabe H, Shirato H, Park CC
  • Journal Title: Breast Cancer Res Volume: 15
  • Peer Reviewed
• [Journal Article] Expression of O6-methylguanine DNA methyltransferase (MGMT) and immunohistochemical analysis of 12 pineal parenchymal tumors. (2012)
  • Author(s): Kanno, H.,Nishihara, H.,Oikawa, M.,Ozaki, Y.,Murata, J.,Sawamura, Y.,Kato, M.,Kubota, K.,Tanino, M. Kimura, T.,Nagashima, K.,Itoh, T.,Tanaka, S.
  • Journal Title: Neuropathology Volume: 32 Issue: 6 Pages: 647-653
  • DOI: 10.1111/j.1440-1789.2012.01315.x
  • NAID: 120005356854
  • Peer Reviewed
• [Journal Article] Diffuse large B-cell lymphoma diagnosed by intracardiac echocardiography-guided cardiac tumor biopsy. (2012)
  • Author(s): Kamiya K, Sakakibara M, Yamada S, Tan M, Furihata T, Kubota K, Tsutsui H.
  • Journal Title: Internal Medicine Volume: 51 Pages: 1043-1047
• [Journal Article] Spontaneous regression of intraocular lymphoma (2012)
  • Author(s): Kase S, Namba K, Jin XH, Kubota KC, Ishida S
  • Journal Title: Ophthalmology Volume: 119 Pages: 1083-1084
• [Presentation] Predictive value of MGMT promoter and LINE-1 methylation status in primary central nervous system diffuse large B-cell lymphoma treated with high-dose MTX and radiotherapy. (2015)
  • Author(s): Hatanaka CK. Hatanaka Y, Fujii K, Kobayashi H, Kannno H, Nishihara H, Mitsuhashi T, Tanaka S, Matsuno Y
  • Organizer: 104th United States and Canadian Academy of Pathology Annual Meeting
  • Place of Presentation: Hynes Convention Center (Boston, USA)
  • Year and Date: 2015-03-21 – 2015-03-27
• [Presentation] 自己免疫性疾患患者に発生した悪性リンパ腫を含むリンパ増殖性疾患に関する臨床病理学的解析 (2014)
  • Author(s): 畑中佳奈子，藤本勝也、辻隆裕、笠原郁美、山本聡、中田匡信、高桑康成、西尾充史、小山田ゆみ子、長谷山美仁、鈴木宏明、米積昌克、野口寛子、酒井基、西原広史、盛暁生、畑中豊、豊島崇徳、松野吉宏
  • Organizer: 第54回日本リンパ網内系学会総会
  • Place of Presentation: 山形国際ホテル（山形市）
  • Year and Date: 2014-06-19 – 2014-06-21
• [Presentation] 中枢神経系原発びまん性大細胞型B細胞性リンパ腫におけるDNAメチレーションの意義に関する検討 (2014)
  • Author(s): 畑中佳奈子，畑中豊、藤井恭子、小林浩之、菅野宏美，西原広史，田中伸哉、三橋智子、松野吉宏
  • Organizer: 第32回日本脳腫瘍病理学会学術集会
  • Place of Presentation: あわぎんホール（徳島市）
  • Year and Date: 2014-05-23 – 2014-05-24
• [Presentation] 中枢神経系原発びまん性大細胞型B細胞性リンパ腫におけるDNAメチル化に関する検討 (2014)
  • Author(s): 畑中佳奈子，畑中豊、小林浩之、菅野宏美，西原広史，田中伸哉、三橋智子、松野吉宏
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 中枢神経系原発びまん性大細胞型B細胞性リンパ腫におけるDNAメチル化に関する解析 (2014)
  • Author(s): 畑中 佳奈子，畑中 豊，小林 浩之，菅野 宏美，西原 広史，田中 伸哉，三橋 智子，松野 吉宏
  • Organizer: 第103回 日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島市）
• [Presentation] 中枢神経系原発びまん性大細胞型B細胞性リンパ腫におけるDNAメチレーションの意義に関する検討 (2014)
  • Author(s): 畑中 佳奈子，畑中 豊，藤井 恭子，小林 浩之，菅野 宏美，西原 広史，田中 伸哉，三橋 智子，松野 吉宏
  • Organizer: 第32回 日本脳腫瘍病理学会
  • Place of Presentation: あわぎんホール（徳島市）
• [Presentation] 自己免疫性疾患患者に発生した悪性リンパ腫を含むリンパ増殖性疾患に関する臨床病理学的解析 (2014)
  • Author(s): 畑中 佳奈子，藤本 勝也，辻 嶐裕，笠原 郁美，山本 聡 ，中田 匡信，高桑 康成，西尾 充史，小山 田ゆみ子，長谷山 美仁，鈴木 宏明，米積 昌克，野口 寛子，酒井 基，西原 広史，盛 暁生，畑中 豊，豊嶋 崇徳，松野 吉宏
  • Organizer: 第54回 リンパ網内系学会
  • Place of Presentation: 山形国際ホテル（山形市）
• [Presentation] Ki-67標識率の画像解析評価におけるプレアナリシスおよびアナリシス因子に関する研究 (2012)
  • Author(s): 森谷純、畑中豊、鈴木雄太、野澤あさひ、丸川活司、久保田佳奈子、三橋智子、松野吉宏
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京都）
• [Presentation] 眼窩IgG4関連疾患を背景に発生したと考えたIgG4陽性形質細胞を伴う節外性濾胞辺縁帯B細胞性リンパ腫の１例 (2012)
  • Author(s): 久保田佳奈子、ヘールナンデス真子、藤田裕美、山田洋介、加瀬諭、畑中豊、高桑恵美、三橋智子、松野吉宏
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京都）