リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「ARID1A loss-of-function induces CpG island methylator phenotype」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

ARID1A loss-of-function induces CpG island methylator phenotype

Yamada, Harumi 京都大学 DOI:10.14989/doctor.k24199

2022.09.26

概要

DNAメチル化などエピゲノムの異常は、ゲノムの突然変異とともに癌の発生や性質に深く関わる。CpGアイランドメチル化形質(CpG island methylator phenotype: CIMP)は、癌細胞においてCpGアイランドが多数メチル化されている現象を指し、胃癌・大腸癌・膠芽腫など様々な癌種で報告されている。CIMPは、予後や薬剤感受性など癌の臨床的特徴と相関し、癌治療戦略において重要な形質である。しかし、膠芽腫や大腸癌を除く癌では、その誘発機構は不明である。

胃癌では、EBV関連胃癌は高度なCIMPを示すことが多く、クロマチンリモデリング因子SWI/SNF複合体の構成因子のひとつであるARID1Aの変異頻度が高い。しかし、SWI/SNF複合体の機能異常がCIMPを誘発するのかについては明らかではない。そこで本研究では、SWI/SNF複合体、なかでもARID1Aの機能異常がCIMP誘発の原因になっているのかを明らかにすることを目的とした。

まず、胃癌臨床検体41例について、71個の癌関連遺伝子の変異解析とゲノム網羅的メチル化解析を行った。その結果、CIMP陽性群ではARID1Aの変異が多く、CIMP陰性群では少ないことがわかった[CIMP陽性群(5/17)vsCIMP陰性群(0/24);p=0.0083]。ARID1A変異のある5例のうち4例はEBV陽性であった。そこで、EBV感染の影響を受けない癌種でTCGAデータを使用して同様の解析を行い、子宮内膜癌[CIMP陽性群(36/49)vsCIMP陰性群(5/25);p=1.65x10-5]や大腸癌[CIMP陽性群(10/26)vsCIMP陰性群(8/51);p=0.044]でも同様の相関を認めた。このことから、ARID1Aの機能異常がCIMPの原因であることが示唆された。

実験的に立証するために、正常細胞株(293FT細胞とGES1細胞)を用いてCRISPR-Cas9システムによりARID1Aノックアウト細胞を樹立し、長期培養後にゲノム網羅的メチル化解析を行った。その結果、ARID1Aノックアウト細胞では、CpGアイランド内外でDNAメチル化異常が誘発され、培養期間依存的にその数が増加することが示された(293FT細胞:0週2,116領域、4週3,481領域、20週5,816領域)。

更に、ARID1A不活化によるDNAメチル化誘発の分子メカニズムを解明するために、DNAメチル化関連酵素(DNAメチル化酵素およびDNA脱メチル化酵素)の発現を解析したが、ARID1Aノックアウトによる発現変化は認めなかった。そこで、DNAメチル化のプレマークであるH3K27me3の変化をクロマチン免疫沈降により解析したところ、親細胞で元々H3K27me3が付いていた部位およびARID1A不活化によりH3K27me3が増加した部位にDNAメチル化が誘発されることがわかった。

ARID1Aを構成要素に含むSWI/SNF複合体はH3K27me3のメチル化酵素であるEZH2と競合することが知られており、SWI/SNF複合体の機能喪失がEZH2活性を上昇させ、H3K27me3の獲得によりその領域のメチル化感受性が上昇すると考えられた。

以上、ARID1Aの機能異常がCIMPを誘発することが明らかとなった。

この論文で使われている画像

参考文献

[1] J.C. Lin, S. Jeong, G. Liang, D. Takai, M. Fatemi, Y.C. Tsai, G. Egger, E.N. Gal-Yam, P.A. Jones, Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG island, Cancer Cell 12 (2007) 432–444.

[2] D.L. Taylor, A.U. Jackson, N. Narisu, G. Hemani, M.R. Erdos, P.S. Chines, A. Swift, J. Idol, J.P. Didion, R.P. Welch, L. Kinnunen, J. Saramies, T.A. Lakka, M. Laakso, J. Tuomilehto, S.C.J. Parker, H.A. Koistinen, G. Davey Smith, M. Boehnke, L. J. Scott, E. Birney, F.S. Collins, Integrative analysis of gene expression, DNA methylation, physiological traits, and genetic variation in human skeletal muscle, Proc. Natl. Acad. Sci. U. S. A. 116 (2019) 10883–10888.

[3] M.V.C. Greenberg, D. Bourc’his, The diverse roles of DNA methylation in mammalian development and disease, Nat. Rev. Mol. Cell Biol. 20 (2019) 590–607.

[4] S.B. Baylin, P.A. Jones, A decade of exploring the cancer epigenome - biological and translational implications, Nat. Rev. Cancer 11 (2011) 726–734.

[5] S.E. Bates, Epigenetic therapies for cancer, N. Engl. J. Med. 383 (2020) 650–663.

[6] A.P. Feinberg, M.A. Koldobskiy, A. Gondor, Epigenetic modulators, modifiers and mediators in cancer aetiology and progression, Nat. Rev. Genet. 17 (2016) 284–299.

[7] J.P. Issa, CpG island methylator phenotype in cancer, Nat. Rev. Cancer 4 (2004) 988–993.

[8] H. Suzuki, E. Yamamoto, R. Maruyama, T. Niinuma, M. Kai, Biological significance of the CpG island methylator phenotype, Biochem. Biophys. Res. Commun. 455 (2014) 35–42.

[9] A.D. Kelly, H. Kroeger, J. Yamazaki, R. Taby, F. Neumann, S. Yu, J.T. Lee, B. Patel, Y. Li, R. He, S. Liang, Y. Lu, M. Cesaroni, S.A. Pierce, S.M. Kornblau, C.E. BuesoRamos, F. Ravandi, H.M. Kantarjian, J. Jelinek, J.P. Issa, A CpG island methylator phenotype in acute myeloid leukemia independent of IDH mutations and associated with a favorable outcome, Leukemia 31 (2017) 2011–2019.

[10] D.J. Weisenberger, G. Liang, H.J. Lenz, DNA methylation aberrancies delineate clinically distinct subsets of colorectal cancer and provide novel targets for epigenetic therapies, Oncogene 37 (2018) 566–577.

[11] Y. Tao, B. Kang, D.A. Petkovich, Y.R. Bhandari, J. In, G. Stein-O’Brien, X. Kong, W. Xie, N. Zachos, S. Maegawa, H. Vaidya, S. Brown, R.W. Chiu Yen, X. Shao, J. Thakor, Z. Lu, Y. Cai, Y. Zhang, I. Mallona, M.A. Peinado, C.A. Zahnow, N. Ahuja, E. Fertig, J.P. Issa, S.B. Baylin, H. Easwaran, Aging-like spontaneous epigenetic silencing facilitates Wnt activation, stemness, and Braf(V600E)-induced tumorigenesis, Cancer Cell 35 (2019) 315–328, e316.

[12] T. Ushijima, H. Suzuki, The origin of CIMP, at last, Cancer Cell 35 (2019) 165–167.

[13] M. Toyota, N. Ahuja, M. Ohe-Toyota, J.G. Herman, S.B. Baylin, J.P. Issa, CpG island methylator phenotype in colorectal cancer, Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 8681–8686.

[14] R. Jover, T.P. Nguyen, L. P´erez-Carbonell, P. Zapater, A. Pay´ a, C. Alenda, E. Rojas, J. Cubiella, F. Balaguer, J.D. Morillas, J. Clofent, L. Bujanda, J.M. Ren˜´e, X. Bessa, R. M. Xicola, D. Nicolas-P ´ ´erez, A. Castells, M. Andreu, X. Llor, C.R. Boland, A. Goel, 5- Fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer, Gastroenterology 140 (2011) 1174–1181.

[15] M. Toyota, N. Ahuja, H. Suzuki, F. Itoh, M. Ohe-Toyota, K. Imai, S.B. Baylin, J. P. Issa, Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype, Cancer Res. 59 (1999) 5438–5442.

[16] S.Y. Park, M.C. Kook, Y.W. Kim, N.Y. Cho, N. Jung, H.J. Kwon, T.Y. Kim, G. H. Kang, CpG island hypermethylator phenotype in gastric carcinoma and its clinicopathological features, Virchows Arch. 457 (2010) 415–422.

[17] H. Zouridis, N. Deng, T. Ivanova, Y. Zhu, B. Wong, D. Huang, Y.H. Wu, Y. Wu, I. B. Tan, N. Liem, V. Gopalakrishnan, Q. Luo, J. Wu, M. Lee, W.P. Yong, L.K. Goh, B. T. Teh, S. Rozen, P. Tan, Methylation subtypes and large-scale epigenetic alterations in gastric cancer, Sci. Transl. Med. 4 (2012) 156ra140.

[18] H. Noushmehr, D.J. Weisenberger, K. Diefes, H.S. Phillips, K. Pujara, B.P. Berman, F. Pan, C.E. Pelloski, E.P. Sulman, K.P. Bhat, R.G. Verhaak, K.A. Hoadley, D. N. Hayes, C.M. Perou, H.K. Schmidt, L. Ding, R.K. Wilson, D. Van Den Berg, H. Shen, H. Bengtsson, P. Neuvial, L.M. Cope, J. Buckley, J.G. Herman, S.B. Baylin, P.W. Laird, K. Aldape, Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma, Cancer Cell 17 (2010) 510–522.

[19] S. Turcan, D. Rohle, A. Goenka, L.A. Walsh, F. Fang, E. Yilmaz, C. Campos, A. W. Fabius, C. Lu, P.S. Ward, C.B. Thompson, A. Kaufman, O. Guryanova, R. Levine, A. Heguy, A. Viale, L.G. Morris, J.T. Huse, I.K. Mellinghoff, T.A. Chan, IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype, Nature 483 (2012) 479–483.

[20] M.J. Dabrowski, B. Wojtas, Global DNA methylation patterns in human gliomas and their interplay with other epigenetic modifications, Int. J. Mol. Sci. 20 (2019).

[21] L. Shen, N. Ahuja, Y. Shen, N.A. Habib, M. Toyota, A. Rashid, J.P. Issa, DNA methylation and environmental exposures in human hepatocellular carcinoma, J. Natl. Cancer Inst. 94 (2002) 755–761.

[22] J. Cheng, D. Wei, Y. Ji, L. Chen, L. Yang, G. Li, L. Wu, T. Hou, L. Xie, G. Ding, H. Li, Y. Li, Integrative analysis of DNA methylation and gene expression reveals hepatocellular carcinoma-specific diagnostic biomarkers, Genome Med. 10 (2018) 42.

[23] G. Li, W. Xu, L. Zhang, T. Liu, G. Jin, J. Song, J. Wu, Y. Wang, W. Chen, C. Zhang, X. Chen, Z. Ding, P. Zhu, B. Zhang, Development and validation of a CIMPassociated prognostic model for hepatocellular carcinoma, EBioMedicine 47 (2019) 128–141.

[24] K. Shinjo, Y. Okamoto, B. An, T. Yokoyama, I. Takeuchi, M. Fujii, H. Osada, N. Usami, Y. Hasegawa, H. Ito, T. Hida, N. Fujimoto, T. Kishimoto, Y. Sekido, Y. Kondo, Integrated analysis of genetic and epigenetic alterations reveals CpG island methylator phenotype associated with distinct clinical characters of lung adenocarcinoma, Carcinogenesis 33 (2012) 1277–1285.

[25] Y. Saito, G. Nagae, N. Motoi, E. Miyauchi, H. Ninomiya, H. Uehara, M. Mun, S. Okumura, F. Ohyanagi, M. Nishio, Y. Satoh, H. Aburatani, Y. Ishikawa, Prognostic significance of CpG island methylator phenotype in surgically resected small cell lung carcinoma, Cancer Sci. 107 (2016) 320–325.

[26] B.P. Whitcomb, D.G. Mutch, T.J. Herzog, J.S. Rader, R.K. Gibb, P.J. Goodfellow, Frequent HOXA11 and THBS2 promoter methylation, and a methylator phenotype in endometrial adenocarcinoma, Clin. Cancer Res. 9 (2003) 2277–2287.

[27] M. Yanokura, K. Banno, M. Adachi, D. Aoki, K. Abe, Genome-wide DNA methylation sequencing reveals miR-663a is a novel epimutation candidate in CIMP-high endometrial cancer, Int. J. Oncol. 50 (2017) 1934–1946.

[28] R. Maruyama, S. Toyooka, K.O. Toyooka, K. Harada, A.K. Virmani, S. Zochbauer- ¨ Müller, A.J. Farinas, F. Vakar-Lopez, J.D. Minna, A. Sagalowsky, B. Czerniak, A. F. Gazdar, Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features, Cancer Res. 61 (2001) 8659–8663.

[29] I. Ibragimova, E. Dulaimi, M.J. Slifker, D.Y. Chen, R.G. Uzzo, P. Cairns, A global profile of gene promoter methylation in treatment-naïve urothelial cancer, Epigenetics 9 (2014) 760–773.

[30] M. Abe, M. Ohira, A. Kaneda, Y. Yagi, S. Yamamoto, Y. Kitano, T. Takato, A. Nakagawara, T. Ushijima, CpG island methylator phenotype is a strong determinant of poor prognosis in neuroblastomas, Cancer Res. 65 (2005) 828–834.

[31] K. Asada, M. Abe, T. Ushijima, Clinical application of the CpG island methylator phenotype to prognostic diagnosis in neuroblastomas, J. Hum. Genet. 58 (2013) 428–433.

[32] D. Capper, N.W. Engel, D. Stichel, M. Lechner, S. Gloss, ¨ S. Schmid, C. Koelsche, D. Schrimpf, J. Niesen, A.K. Wefers, D.T.W. Jones, M. Sill, O. Weigert, K.L. Ligon, A. Olar, A. Koch, M. Forster, S. Moran, O.M. Tirado, M. S´ ainz-Jaspeado, J. Mora, M. Esteller, J. Alonso, X.G. Del Muro, W. Paulus, J. Felsberg, G. Reifenberger, M. Glatzel, S. Frank, C.M. Monoranu, V.J. Lund, A. von Deimling, S. Pfister, R. Buslei, J. Ribbat-Idel, S. Perner, V. Gudziol, M. Meinhardt, U. Schüller, DNA methylation-based reclassification of olfactory neuroblastoma, Acta Neuropathol. 136 (2018) 255–271.

[33] M. Tokunaga, C.E. Land, Y. Uemura, T. Tokudome, S. Tanaka, E. Sato, Epstein-Barr virus in gastric carcinoma, Am. J. Pathol. 143 (1993) 1250–1254.

[34] A.P. Burke, T.S. Yen, K.M. Shekitka, L.H. Sobin, Lymphoepithelial carcinoma of the stomach with Epstein-Barr virus demonstrated by polymerase chain reaction, Mod. Pathol. 3 (1990) 377–380.

[35] M. Fukayama, R. Hino, H. Uozaki, Epstein-Barr virus and gastric carcinoma: virushost interactions leading to carcinoma, Cancer Sci. 99 (2008) 1726–1733.

[36] K. Matsusaka, A. Kaneda, G. Nagae, T. Ushiku, Y. Kikuchi, R. Hino, H. Uozaki, Y. Seto, K. Takada, H. Aburatani, M. Fukayama, Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes, Cancer Res. 71 (2011) 7187–7197.

[37] T.V. Bass Aj, I. Shmulevich, S.M. Reynolds, M. Miller, B. Bernard, T. Hinoue, P. W. Laird, C. Curtis, H. Shen, D.J. Weisenberger, N. Schultz, R. Shen, N. Weinhold, D.P. Kelsen, R. Bowlby, A. Chu, K. Kasaian, A.J. Mungall, A.G. Robertson, P. Sipahimalani, A.D. Cherniack, G. Getz, Y. Liu, M.S. Noble, C. Pedamallu, C. Sougnez, A. Taylor-Weiner, R. Akbani, J.S. Lee, W. Liu, G.B. Mills, D. Yang, W. Zhang, A. Pantazi, M. Parfenov, M. Gulley, M.B. Piazuelo, B.G. Schneider, J. Kim, A. Boussioutas, M. Sheth, J.A. Demchok, C.S. Rabkin, J.E. Willis, S. Ng, K. Garman, D.G. Beer, A. Pennathur, B.J. Raphael, H.T. Wu, R. Odze, H.K. Kim, J. Bowen, K.M. Leraas, T.M. Lichtenberg, S. Weaver, M. McLellan, M. Wiznerowicz, R. Sakai, G. Getz, C. Sougnez, M.S. Lawrence, K. Cibulskis, L. Lichtenstein, S. Fisher, S.B. Gabriel, E.S. Lander, L. Ding, B. Niu, A. Ally, M. Balasundaram, I. Birol, R. Bowlby, D. Brooks, Y.S. Butterfield, R. Carlsen, A. Chu, J. Chu, E. Chuah, H.J. Chun, A. Clarke, N. Dhalla, R. Guin, R.A. Holt, S.J. Jones, K. Kasaian, D. Lee, H.A. Li, E. Lim, Y. Ma, M.A. Marra, M. Mayo, R.A. Moore, A.J. Mungall, K. L. Mungall, K. Ming Nip, A.G. Robertson, J.E. Schein, P. Sipahimalani, A. Tam, N. Thiessen, R. Beroukhim, S.L. Carter, A.D. Cherniack, J. Cho, K. Cibulskis, D. DiCara, S. Frazer, S. Fisher, S.B. Gabriel, N. Gehlenborg, D.I. Heiman, J. Jung, J. Kim, E.S. Lander, M.S. Lawrence, L. Lichtenstein, P. Lin, M. Meyerson, A. I. Ojesina, C. Sekhar Pedamallu, G. Saksena, S.E. Schumacher, C. Sougnez, P. Stojanov, B. Tabak, A. Taylor-Weiner, D. Voet, M. Rosenberg, T.I. Zack, H. Zhang, L. Zou, A. Protopopov, N. Santoso, M. Parfenov, S. Lee, J. Zhang, H. S. Mahadeshwar, J. Tang, X. Ren, S. Seth, L. Yang, A.W. Xu, X. Song, A. Pantazi, R. Xi, C.A. Bristow, A. Hadjipanayis, J. Seidman, L. Chin, P.J. Park, R. Kucherlapati, R. Akbani, S. Ling, W. Liu, A. Rao, J.N. Weinstein, S.B. Kim, J. S. Lee, Y. Lu, G. Mills, P.W. Laird, T. Hinoue, D.J. Weisenberger, M.S. Bootwalla, P. H. Lai, H. Shen, T. Triche Jr., D.J. Van Den Berg, S.B. Baylin, J.G. Herman, G. Getz, L. Chin, Y. Liu, B.A. Murray, M.S. Noble, B.A. Askoy, G. Ciriello, G. Dresdner, J. Gao, B. Gross, A. Jacobsen, W. Lee, R. Ramirez, C. Sander, N. Schultz, Y. Senbabaoglu, R. Sinha, S.O. Sumer, Y. Sun, N. Weinhold, V. Thorsson, B. Bernard, L. Iype, R.W. Kramer, R. Kreisberg, M. Miller, S.M. Reynolds, H. Rovira, N. Tasman, I. Shmulevich, S. Ng, D. Haussler, J.M. Stuart, R. Akbani, S. Ling, W. Liu, A. Rao, J.N. Weinstein, R.G. Verhaak, G.B. Mills, M.D. Leiserson, B. J. Raphael, H.T. Wu, B.S. Taylor, A.D. Black, J. Bowen, J.A. Carney, J.M. GastierFoster, C. Helsel, K.M. Leraas, T.M. Lichtenberg, C. McAllister, N.C. Ramirez, T. R. Tabler, L. Wise, E. Zmuda, R. Penny, D. Crain, J. Gardner, K. Lau, E. Curely, D. Mallery, S. Morris, J. Paulauskis, T. Shelton, C. Shelton, M. Sherman, C. Benz, J. H. Lee, K. Fedosenko, G. Manikhas, O. Potapova, O. Voronina, D. Belyaev, O. Dolzhansky, W.K. Rathmell, J. Brzezinski, M. Ibbs, K. Korski, W. Kycler, R. La´zniak, E. Leporowska, A. Mackiewicz, D. Murawa, P. Murawa, A. Spychała, W. M. Suchorska, H. Tatka, M. Teresiak, M. Wiznerowicz, R. Abdel-Misih, J. Bennett, J. Brown, M. Iacocca, B. Rabeno, S.Y. Kwon, R. Penny, J. Gardner, A. Kemkes, D. Mallery, S. Morris, T. Shelton, C. Shelton, E. Curley, I. Alexopoulou, J. Engel, J. Bartlett, M. Albert, D.Y. Park, R. Dhir, J. Luketich, R. Landreneau, Y.Y. Janjigian, D.P. Kelsen, E. Cho, M. Ladanyi, L. Tang, S.J. McCall, Y.S. Park, J.H. Cheong, J. Ajani, M.C. Camargo, S. Alonso, B. Ayala, M.A. Jensen, T. Pihl, R. Raman, J. Walton, Y. Wan, J.A. Demchok, G. Eley, K.R. Mills Shaw, M. Sheth, R. Tarnuzzer, Z. Wang, L. Yang, J.C. Zenklusen, T. Davidsen, C.M. Hutter, H.J. Sofia, R. Burton, S. Chudamani, J. Liu, Comprehensive molecular characterization of gastric adenocarcinoma, Nature 513 (2014) 202–209.

[38] H. Namba-Fukuyo, S. Funata, K. Matsusaka, M. Fukuyo, B. Rahmutulla, Y. Mano, M. Fukayama, H. Aburatani, A. Kaneda, TET2 functions as a resistance factor against DNA methylation acquisition during Epstein-Barr virus infection, Oncotarget 7 (2016) 81512–81526.

[39] S. Funata, K. Matsusaka, R. Yamanaka, S. Yamamoto, A. Okabe, M. Fukuyo, H. Aburatani, M. Fukayama, A. Kaneda, Histone modification alteration coordinated with acquisition of promoter DNA methylation during Epstein-Barr virus infection, Oncotarget 8 (2017) 55265–55279.

[40] A. Okabe, K.K. Huang, K. Matsusaka, M. Fukuyo, M. Xing, X. Ong, T. Hoshii, G. Usui, M. Seki, Y. Mano, B. Rahmutulla, T. Kanda, T. Suzuki, S.Y. Rha, T. Ushiku, M. Fukayama, P. Tan, A. Kaneda, Cross-species chromatin interactions drive transcriptional rewiring in Epstein-Barr virus-positive gastric adenocarcinoma, Nat. Genet. 52 (2020) 919–930.

[41] K. Kase, M. Saito, S. Nakajima, D. Takayanagi, K. Saito, L. Yamada, M. Ashizawa, H. Nakano, H. Hanayama, H. Onozawa, H. Okayama, H. Endo, S. Fujita, W. Sakamoto, Z. Saze, T. Momma, K. Mimura, S. Ohki, K. Shiraishi, T. Kohno, K. Kono, ARID1A deficiency in EBV-positive gastric cancer is partially regulated by EBV-encoded miRNAs, but not by DNA promotor hypermethylation, Carcinogenesis 42 (2021) 21–30.

[42] Y. Yoda, H. Takeshima, T. Niwa, J.G. Kim, T. Ando, R. Kushima, T. Sugiyama, H. Katai, H. Noshiro, T. Ushijima, Integrated analysis of cancer-related pathways affected by genetic and epigenetic alterations in gastric cancer, Gastric Cancer 18 (2015) 65–76.

[43] R.F. Ambinder, R.B. Mann, Detection and characterization of Epstein-Barr virus in clinical specimens, Am. J. Pathol. 145 (1994) 239–252.

[44] H. Takeshima, T. Niwa, S. Yamashita, T. Takamura-Enya, N. Iida, M. Wakabayashi, S. Nanjo, M. Abe, T. Sugiyama, Y.J. Kim, T. Ushijima, TET repression and increased DNMT activity synergistically induce aberrant DNA methylation, J. Clin. Invest. 130 (2020) 5370–5379.

[45] J.G. Kim, H. Takeshima, T. Niwa, E. Rehnberg, Y. Shigematsu, Y. Yoda, S. Yamashita, R. Kushima, T. Maekita, M. Ichinose, H. Katai, W.S. Park, Y.S. Hong, C.H. Park, T. Ushijima, Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers, Cancer Lett. 330 (2013) 33–40.

[46] L. Zong, N. Hattori, Y. Yoda, S. Yamashita, H. Takeshima, T. Takahashi, M. Maeda, H. Katai, S. Nanjo, T. Ando, Y. Seto, T. Ushijima, Establishment of a DNA methylation marker to evaluate cancer cell fraction in gastric cancer, Gastric Cancer 19 (2016) 361–369.

[47] N. Iida, Y. Okuda, O. Ogasawara, S. Yamashita, H. Takeshima, T. Ushijima, MACON: a web tool for computing DNA methylation data obtained by the Illumina Infinium Human DNA methylation BeadArray, Epigenomics 10 (2018) 249–258.

[48] T. Nakamura, S. Yamashita, K. Fukumura, J. Nakabayashi, K. Tanaka, K. Tamura, K. Tateishi, M. Kinoshita, S. Fukushima, H. Takami, K. Fukuoka, K. Yamazaki, Y. Matsushita, M. Ohno, Y. Miyakita, S. Shibui, A. Kubo, T. Shuto, S. Kocialkowski, S. Yamanaka, A. Mukasa, T. Sasayama, K. Mishima, T. Maehara, N. Kawahara, M. Nagane, Y. Narita, H. Mano, T. Ushijima, K. Ichimura, Genome-wide DNA methylation profiling identifies primary central nervous system lymphoma as a distinct entity different from systemic diffuse large B-cell lymphoma, Acta Neuropathol. 133 (2017) 321–324.

[49] H. Takeshima, T. Niwa, T. Takahashi, M. Wakabayashi, S. Yamashita, T. Ando, Y. Inagawa, H. Taniguchi, H. Katai, T. Sugiyama, T. Kiyono, T. Ushijima, Frequent involvement of chromatin remodeler alterations in gastric field cancerization, Cancer Lett. 357 (2015) 328–338.

[50] H. Takeshima, S. Yamashita, T. Shimazu, T. Niwa, T. Ushijima, The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands, Genome Res. 19 (2009) 1974–1982.

[51] B. Langmead, S.L. Salzberg, Fast gapped-read alignment with Bowtie 2, Nat. Methods 9 (2012) 357–359.

[52] Y. Zhang, T. Liu, C.A. Meyer, J. Eeckhoute, D.S. Johnson, B.E. Bernstein, C. Nusbaum, R.M. Myers, M. Brown, W. Li, X.S. Liu, Model-based analysis of ChIPseq (MACS), Genome Biol. 9 (2008) R137.

[53] J.T. Robinson, H. Thorvaldsdottir, ´ W. Winckler, M. Guttman, E.S. Lander, G. Getz, J.P. Mesirov, Integrative genomics viewer, Nat. Biotechnol. 29 (2011) 24–26.

[54] S. Enomoto, T. Maekita, T. Tsukamoto, T. Nakajima, K. Nakazawa, M. Tatematsu, M. Ichinose, T. Ushijima, Lack of association between CpG island methylator phenotype in human gastric cancers and methylation in their background noncancerous gastric mucosae, Cancer Sci. 98 (2007) 1853–1861.

[55] M.R. Wilson, J.J. Reske, J. Holladay, G.E. Wilber, M. Rhodes, J. Koeman, M. Adams, B. Johnson, R.W. Su, N.R. Joshi, A.L. Patterson, H. Shen, R.E. Leach, J. M. Teixeira, A.T. Fazleabas, R.L. Chandler, ARID1A and PI3-kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion, Nat. Commun. 10 (2019) 3554.

[56] J.N. Wu, C.W. Roberts, ARID1A mutations in cancer: another epigenetic tumor suppressor? Cancer Discov. 3 (2013) 35–43.

[57] M. Safran, I. Dalah, J. Alexander, N. Rosen, T. Iny Stein, M. Shmoish, N. Nativ, I. Bahir, T. Doniger, H. Krug, A. Sirota-Madi, T. Olender, Y. Golan, G. Stelzer, A. Harel, D. Lancet, GeneCards Version 3: the Human Gene Integrator, Database, Oxford), 2010, p. baq020, 2010.

[58] J.E. Ohm, K.M. McGarvey, X. Yu, L. Cheng, K.E. Schuebel, L. Cope, H. P. Mohammad, W. Chen, V.C. Daniel, W. Yu, D.M. Berman, T. Jenuwein, K. Pruitt, S.J. Sharkis, D.N. Watkins, J.G. Herman, S.B. Baylin, A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing, Nat. Genet. 39 (2007) 237–242.

[59] Y. Schlesinger, R. Straussman, I. Keshet, S. Farkash, M. Hecht, J. Zimmerman, E. Eden, Z. Yakhini, E. Ben-Shushan, B.E. Reubinoff, Y. Bergman, I. Simon, H. Cedar, Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer, Nat. Genet. 39 (2007) 232–236.

[60] M. Widschwendter, H. Fiegl, D. Egle, E. Mueller-Holzner, G. Spizzo, C. Marth, D. J. Weisenberger, M. Campan, J. Young, I. Jacobs, P.W. Laird, Epigenetic stem cell signature in cancer, Nat. Genet. 39 (2007) 157–158.

[61] H. Takeshima, D. Ikegami, M. Wakabayashi, T. Niwa, Y.J. Kim, T. Ushijima, Induction of aberrant trimethylation of histone H3 lysine 27 by inflammation in mouse colonic epithelial cells, Carcinogenesis 33 (2012) 2384–2390.

[62] T. Shimizu, H. Marusawa, Y. Matsumoto, T. Inuzuka, A. Ikeda, Y. Fujii, S. Minamiguchi, S. Miyamoto, T. Kou, Y. Sakai, J.E. Crabtree, T. Chiba, Accumulation of somatic mutations in TP53 in gastric epithelium with Helicobacter pylori infection, Gastroenterology 147 (2014) 407–417, e403.

[63] L. Tran, J.F. Xiao, N. Agarwal, J.E. Duex, D. Theodorescu, Advances in bladder cancer biology and therapy, Nat. Rev. Cancer 21 (2021) 104–121.

[64] K.C. Helming, X. Wang, B.G. Wilson, F. Vazquez, J.R. Haswell, H.E. Manchester, Y. Kim, G.V. Kryukov, M. Ghandi, A.J. Aguirre, Z. Jagani, Z. Wang, L.A. Garraway, W.C. Hahn, C.W. Roberts, ARID1B is a specific vulnerability in ARID1A-mutant cancers, Nat. Med. 20 (2014) 251–254.

[65] B.G. Wilson, X. Wang, X. Shen, E.S. McKenna, M.E. Lemieux, Y.J. Cho, E. C. Koellhoffer, S.L. Pomeroy, S.H. Orkin, C.W. Roberts, Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation, Cancer Cell 18 (2010) 316–328.

[66] B.G. Bitler, K.M. Aird, A. Garipov, H. Li, M. Amatangelo, A.V. Kossenkov, D. C. Schultz, Q. Liu, M. Shih Ie, J.R. Conejo-Garcia, D.W. Speicher, R. Zhang, Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1Amutated cancers, Nat. Med. 21 (2015) 231–238.

[67] S. Yamashita, S. Nanjo, E. Rehnberg, N. Iida, H. Takeshima, T. Ando, T. Maekita, T. Sugiyama, T. Ushijima, Distinct DNA methylation targets by aging and chronic inflammation: a pilot study using gastric mucosa infected with Helicobacter pylori, Clin. Epigenet. 11 (2019) 191.

[68] M. Yu, W.D. Hazelton, G.E. Luebeck, W.M. Grady, Epigenetic aging: more than just a clock when it comes to cancer, Cancer Res. 80 (2020) 367–374.

[69] A.R. Maiuri, M. Peng, R. Podicheti, S. Sriramkumar, C.M. Kamplain, D.B. Rusch, C. E. DeStefano Shields, C.L. Sears, H.M. O’Hagan, Mismatch repair proteins initiate epigenetic alterations during inflammation-driven tumorigenesis, Cancer Res. 77 (2017) 3467–3478.

[70] M. Weber, I. Hellmann, M.B. Stadler, L. Ramos, S. Pa¨¨ abo, M. Rebhan, D. Schübeler, Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome, Nat. Genet. 39 (2007) 457–466.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る