ヘルペスウイルス関連リンパ腫を中心とする日本人リンパ腫の特性の解明

• Project/Area Number: 12218207
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: 森 茂郎 東京大学, 医科学研究所, 教授 (30010424)
• Co-Investigator(Kenkyū-buntansha): 佐藤 均 東京大学, 医科学研究所, 助手 (70183829) ; 中村 栄男 愛知がんセンター病院, 遺伝子病理診断部, 部長(研究職) (80180363)
• Project Period (FY): 2000 – 2004
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥45,700,000 (Direct Cost: ¥45,700,000); Fiscal Year 2003: ¥11,000,000 (Direct Cost: ¥11,000,000); Fiscal Year 2002: ¥11,700,000 (Direct Cost: ¥11,700,000); Fiscal Year 2001: ¥12,000,000 (Direct Cost: ¥12,000,000); Fiscal Year 2000: ¥11,000,000 (Direct Cost: ¥11,000,000)
• Keywords: ウィルス / 癌 / ゲノム / 細胞・組織 / 病理学 / 悪性リンパ腫 / 胚中心 / Epstein-Barrウィルス / 8型ヘルペスウィルス / bcl-6 / ホジキン病 / Epstein-Barrウイルス / 8型ヘルペスウイルス / bcl16 / ヘルペスウイルス / Epstein Barrウイルス

Research Abstract

我々は近年、日本人ホジキン病の特性について研究している過程で偶然に、正常日本人のEBV感染率が、以前言われていたような小児で99%という値ではないと考えさせるデータを得たので、これを確認する疫学研究を行い、6-10歳児の抗体保有率が1990年以降、95%から70%以下に急激に低下しつつあることを見出した。この陽性率の変化を統計数学的に処理したところ、2005年以降、この世代の児童の抗体保有率は50%を切ることが計算上推定された。EBVはいうまでもなく我が国の悪性リンパ腫、胃癌などの発生に大きな役割を果たしている。従って小児におけるこのような感染率の変化は今後の日本人におけるEBV関連リンパ腫の発生の低下という現象を推定させるものであると考えた。そこで、多数の日本人悪性リンパ腫について、腫瘍細胞中にEBV transcriptの同定を行うことによって、我が国のEBV関連リンパ腫の現時点での実体を明らかにすることを試み、さらに、今後30年間の小児のEBV抗体陽性率を参考に、それらの各亜型の発生の推移を推定した。今回の検索の結果として、我が国では今後それぞれの時代に小児期であるポピュレーションが成人になる年度において、EBV関連非ホジキンリンパ腫は漸減し、2160年頃にはEBV関連リンパ腫総体は現在の3/4以下に減少するということが推定された。なお、EBV関連ホジキン病についてはこの推定が出来なかった。この間の他の成果として、EBV関連リンパ腫の新たなマーカーとしてLMP2aの発現動態を明らかにしたこと(未発表)を付け加える。

Research Products

• [Publications] Nakada C, Tsukamoto Y, Oka A, Nonaka I, Takeda T, Sato K, Mori S, Ito H, Moriyama M.: "Cardiac restricted ankyrin repeated protein (CARP) is differentially induced in Duchnne end congenital muscular dystrophy"Lab Invest. 83. 711-719 (2003)
• [Publications] Nakae S, Saijo S, Horai R, Sudo K, Mori S., Iwakura Y.: "IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient In IL-1 receptor antagonist"Proc Natl AcadSci USA. 100. 5986-5990 (2003)
• [Publications] Ree HJ, Ohsima K, Aozasa K, Takeuchi K, Kim CW, Yang WI, Huh JY, Lee SS.Ko, YH.Kwon MS, Cho EY, Choi YL, Rhee JC, Kikuchi M, Mori S.: "Detection of germinal center B-cell lymphoma in archival specimens : critical evaluation of Bcl-6 protein expression in diffuse large B-cell lymphoma of the tonsil"Human Pathology.. 34. 610-616 (2003)
• [Publications] Yoshide Y, Nakamura T, Komoda M, Satoh H, Suzuki T, Tsuzuku JK, Miyasake T, Yoshida EH, Umemori H, Kunisaki RK, Tani K, Ishii S, Mori S, Suganuma M, Noda T, Yamamoto T.: "Mice lacking a transcriptional corepressor Tob are predisposed to cancer"Genes & Development. 17. 171201-171206 (2003)
• [Publications] Ito E., Honma R., Imai J., Azuma S., Kanno T., Mori S., Yoshie O., Nishio J., Iwasaki H., Yoshida K., Gohda J., Inoue J., Watanabe S., Semba K.: "A tetraspanin-family protein, T-cell acute lymphoblastic leukemia-associated antigen 1, is induced by the Ewing's sarcoma-Wiims'tumor 1 fusion protein of desmoplastic small round-cell tumor"Am J Pathol.. 163. 2165-2172 (2003)
• [Publications] Fujino Y., Satoh H., Hisasue M., Masuda K., Ohno K., Tsujimoto H.: "Detection of the integrated feline leukemia viruses in a cat lymphold tumor cell line by fluorescence in situ hybridization"J.Hered.. 94. 251-255 (2003)
• [Publications] Satoh H., Fujiwara M., Fukami T., Fukuhara H., Murakami Y.: "Comparative assignments of the TSLC1 and TSLC1-like tumor suppressor genes, TSLL1 and TSLL2, to rat chromosomes by fluorescence in situ hybridization"Bull.Nippon Vet.Anim.Sci.Univ.. 52. 24-28 (2003)
• [Publications] Yamada T., Suzuki M., Satoh H., Kihara NF., Nakano H., Oikawa T.: "Effects of PU.1-induced mouse calcium-calmodulin-dependent kinase I-like kinase (CKLIK) on apoptosis of murine erythroleukemia cells"Exp.Cell.Res.. 294. 39-50 (2003)
• [Publications] Fujiwara M., Tsukamoto Y., Miyazaki A., Moriyama M., Satoh H: "Assignment of the murine ankyrin-repeeted protein gene (Ankrd2) to mouse chromosome 19C3→D1 and rat chromosome 1q51→q53 by fluorescence in situ hybridization"Cytogenet.Genome Res.. (in press).
• [Publications] Maekawa I, Aoki N, Shiota M, Nonaka Y, Mori S: "Establishment and characterization of Epstein-Barr Virus-bearing T cell lymphoma occurining in nose"Jpn J Cancer Res. 93. 61-69 (2002)
• [Publications] Kakiuchi c, Ishida T, Sato H, Katano H, Ishiko T, Mukai H, Kogi M, Kasuga N, Takeuchi K, Yamane K, Fukayama M, Mori S: "Secretion of interleukin-6 and vascular endothelial growth factor by spindle cell sarcoma complicating with Castleman's disease, so-called Vascular Neoplasia"J Pathol. 197. 264-271 (2002)
• [Publications] Ishiguro N, Ishida T, Takeuchi K, Osaki M, Araki N, Okada E, Takahashi S, Saito M, Watanabe M, Nakada C, Tsukamoto Y, Sato K, Ito K, Fukayama M, Mori S, Ito H, Moriyama M: "CARP, a putative genetic marker for cardiac hypertrophy, and its new homologue, ARPP, are differentially expressed in heart, skeletal muscle and rhabdomyosarcoma"Am J Pathol. 160. 1767-1778 (2002)
• [Publications] Kanno T, Endo H, Takeuchi K, Morishita Y, Fukayama M, Mori S: "High expression of methionine aminopeptidase type 2 in germinal center B cells and their neoplastic counterparts"Lab Invest. 82. 893-901
• [Publications] Endo H, Takenaga K, Kanno T, Satoh H, Mori S: "Methionine aminopeptidase 2 is a new target for the metastasis-associated protein, S100A4"J Biol Chem. 277. 26396-2640 (2002)
• [Publications] Katano H, Mori S: "AIDS-related lymphoma, in Epstein-Barr virus and human cancer, ed. by Tanaka K and Sixbey JW"Current Top Microbiol Immunol. 258. 121-138 (2001)
• [Publications] Takeuchi K, Morishita Y, Mukayama M, Mori S: "Rapid decrease of EBV-infected cases among Japanese Hodgkin's diseases in recent decades"Brit J Hematol. 113. 429-431 (2001)
• [Publications] Sakurada S, Katano H, Sata T, Ohkuni H, Watanabe T, Mori S: "Effective human herpesvirus 8 infection of human umbilical vein endothelial cells by cell-mediated transmission"J Virol. 75. 7717-7722 (2001)
• [Publications] Kaneita Y, Yoshida S, Ishiguro N, Sawada U, Hone T, Mori S: "Detection of reciprocal fusion 5'-BCL6/partner-3' transcripts in lymphomas exhibiting reciprocal BCL6 translocations"Brit J Hematol. 113. 803-806 (2001)
• [Publications] Suda T, Katano H, Delsol G, Takeuchi S, Nakamura T, Shiota M, Sata T, Higashihara M, Mori S: "HHV-8 infection status of AIDS-unrelated and AIDS-associated mucticentric Castleman's disease"Pathology International. 51. 671-679 (2001)
• [Publications] Kakiuchi c, Ishida T, Sato H, Katano H, Ishiko T, Mukai H, Kogi M, Kasuga N, Takeuchi K, Yamane K, Fukayama M, Mori S: "Secretion of interleukin-6 and vascular endothelial growthfactor by spindle cell sarcoma complicating with Castleman's disease, so-called Vascular Neoplasia"J Pathol.
• [Publications] Tanaka R,Satoh H,Moriyama M,Satoh K,Morishita Y,Yoshida S,Watanabe T,Nakamura Y and Mori S: "Intronic U50 small nucleolar RNA (snoRNA) host gene of no protein-coding potenitial is mapped at the chromosome breakpoint t(3;6)(q27;q15) of human B-cell lymphoma"Genes to Cells. 5. 277-287 (2000)
• [Publications] Katano H,Suda T,Morishita Y,Yamamoto K,Hoshino Y,Nakamura K,Tachikawa N,Sata T,Hamabuchi H,Iwamoto A,Mori S: "HHV-8-carrying solid B-cell lymphomas take anaplastic large cell morphology"Modern Pathology. 13. 77-85 (2000)
• [Publications] Mori S: "Cooperative Study of Lymphoma Study Group of Japanese Pathologists (Sponsored by Mori S) : WHO Classification of Malignant Lymphomas in Japan : Incidence of Recently Recognized Entities"Pathology International. 50. 696-702 (2000)
• [Publications] Katano H,Sato Y,Kurata T,Mori S and Sata T: "Expression and localization of human herpesvirus 8-encoded proteins in primary effusion lymphoma, Kaposi's sarcoma and multicentric Castneman's disease"Virology. 269. 335-344 (2000)
• [Publications] Kojima M,Nakamura S,Moriahita Y,Itoh H,Yoshida K,Ohno Y,Oyama T,Asano S,Joshita T,Mori S,Suchi T,Masawa N: "Reactive follicular hyperplasia in the lymph node lesions from systemic lupus eryhematosus patients : A clinicopathological and immunohistologial study of 21 cases"Pathology International. 50. 304-12 (2000)
• [Publications] Izumo T,Maseki N,Mori S,Tsuchiya E: "Practical utility of the Revised European-American Classification of lymphoid neoplasms for Japanese non-Hodgkin's lymphomas"Jpn J Cancer Res. 91. 351-60 (2000)
• [Publications] Katano H,Iwasaki T,Baba N,Terai M,Mori S,Iwamoto A,Kurata T and Sata T: "Identification of antigenic proteins encoded by human herpesvirus 8 and the seroprevalence in the general population and among patients with and without Kaposi : s sarcoma "J Virol. 74. 3478-85 (2000)
• [Publications] Katano H and Mori S: "AIDS-related lymphoma, in Epstein-Barr virus and human cancer, ed .by Tanaka K and Sixbey JW"Current Top Microbiol Immunol. (in press). (2001)
• [Publications] "Rapid decrease of EBV-infected cases among Japanse Hodgkin's diseases in recent decades"Brit J Hematol. (in press). (2001)