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Volumn 120, Issue 11, 2012, Pages 2280-2289

Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas

Author keywords

[No Author keywords available]

Indexed keywords

HYBRID PROTEIN; PROTEIN P53; PROTEIN P63;

EID: 84866363110     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2012-03-419937     Document Type: Article
Times cited : (196)

References (48)
  • 1
    • 6944248818 scopus 로고    scopus 로고
    • Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification
    • DOI 10.1093/annonc/mdh392
    • Savage KJ, Chhanabhai M, Gascoyne RD, Connors JM. Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification. Ann Oncol. 2004; 15(10):1467-1475. (Pubitemid 39409735)
    • (2004) Annals of Oncology , vol.15 , Issue.10 , pp. 1467-1475
    • Savage, K.J.1    Chhanabhai, M.2    Gascoyne, R.D.3    Connors, J.M.4
  • 2
    • 47049084821 scopus 로고    scopus 로고
    • ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: Report from the International Peripheral T-Cell Lymphoma Project
    • Savage KJ, Harris NL, Vose JM, et al. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood. 2008; 111(12):5496-5504.
    • (2008) Blood , vol.111 , Issue.12 , pp. 5496-5504
    • Savage, K.J.1    Harris, N.L.2    Vose, J.M.3
  • 3
    • 69149089720 scopus 로고    scopus 로고
    • WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
    • Bosman F, Jaffe E, Lakhani S, Ohgaki H, eds. 4 Ed. Lyon, France: International Agency for Research on Cancer
    • Swerdlow S, Campo E, Harris N, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. In: Bosman F, Jaffe E, Lakhani S, Ohgaki H, eds. World Health Organization Classification of Tumours. 4 Ed. Lyon, France: International Agency for Research on Cancer; 2008.
    • (2008) World Health Organization Classification of Tumours
    • Swerdlow, S.1    Campo, E.2    Harris, N.3
  • 5
    • 78650026375 scopus 로고    scopus 로고
    • ALK inhibition for non-small cell lung cancer: From discovery to therapy in record time
    • Gerber DE, Minna JD. ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time. Cancer Cell. 2010;18(6):548-551.
    • (2010) Cancer Cell , vol.18 , Issue.6 , pp. 548-551
    • Gerber, D.E.1    Minna, J.D.2
  • 6
    • 62549122477 scopus 로고    scopus 로고
    • Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas
    • Feldman AL, Law M, Remstein ED, et al. Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas. Leukemia. 2009;23(3):574-580.
    • (2009) Leukemia , vol.23 , Issue.3 , pp. 574-580
    • Feldman, A.L.1    Law, M.2    Remstein, E.D.3
  • 7
    • 78751692894 scopus 로고    scopus 로고
    • Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively-parallel genomic sequencing
    • Feldman AL, Dogan A, Smith DI, et al. Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively-parallel genomic sequencing. Blood. 2011;117(3):915-919.
    • (2011) Blood , vol.117 , Issue.3 , pp. 915-919
    • Feldman, A.L.1    Dogan, A.2    Smith, D.I.3
  • 8
    • 79953323634 scopus 로고    scopus 로고
    • Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: A multicenter study of 204 skin biopsies
    • Wada DA, Law ME, Hsi ED, et al. Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies. Mod Pathol. 2011;24(4):596-605.
    • (2011) Mod Pathol , vol.24 , Issue.4 , pp. 596-605
    • Wada, D.A.1    Law, M.E.2    Hsi, E.D.3
  • 9
    • 79955679824 scopus 로고    scopus 로고
    • Role of p63 in cancer development
    • Graziano V, De Laurenzi V. Role of p63 in cancer development. Biochim Biophys Acta. 2011; 1816(1):57-66.
    • (2011) Biochim Biophys Acta , vol.1816 , Issue.1 , pp. 57-66
    • Graziano, V.1    De Laurenzi, V.2
  • 10
    • 48649101217 scopus 로고    scopus 로고
    • Incidence of TCR and TCL1 gene translocations and isochromosome 7q in peripheral T-cell lymphomas using fluorescence in situ hybridization
    • Feldman AL, Law M, Grogg KL, et al. Incidence of TCR and TCL1 gene translocations and isochromosome 7q in peripheral T-cell lymphomas using fluorescence in situ hybridization. Am J Clin Pathol. 2008;130(2):178-185.
    • (2008) Am J Clin Pathol , vol.130 , Issue.2 , pp. 178-185
    • Feldman, A.L.1    Law, M.2    Grogg, K.L.3
  • 12
    • 46949111833 scopus 로고    scopus 로고
    • Germinal center B (GCB) and non-GCB cell-like diffuse large B cell lymphomas have similar outcomes following autologous haematopoietic stem cell transplantation
    • DOI 10.1111/j.1365-2141.2008.07207.x
    • Costa LJ, Feldman AL, Micallef IN, et al. Germinal center B (GCB) and non-GCB cell-like diffuse large B cell lymphomas have similar outcomes following autologous haematopoietic stem cell transplantation. Br J Haematol. 2008;142(3):404-412. (Pubitemid 351962182)
    • (2008) British Journal of Haematology , vol.142 , Issue.3 , pp. 404-412
    • Costa, L.J.1    Feldman, A.L.2    Micallef, I.N.3    Inwards, D.J.4    Johnston, P.B.5    Porrata, L.F.6    Ansell, S.M.7
  • 13
    • 77951203643 scopus 로고    scopus 로고
    • Development and validation of a comprehensive mutation and deletion detection assay for SDHB, SDHC, and SDHD
    • Milosevic D, Lundquist P, Cradic K, et al. Development and validation of a comprehensive mutation and deletion detection assay for SDHB, SDHC, and SDHD. Clin Biochem. 2010;43(7-8): 700-704.
    • (2010) Clin Biochem , vol.43 , Issue.7-8 , pp. 700-704
    • Milosevic, D.1    Lundquist, P.2    Cradic, K.3
  • 14
    • 22144489899 scopus 로고    scopus 로고
    • INK4a/ARF: A multifunctional tumor suppressor locus
    • DOI 10.1016/j.mrfmmm.2004.08.021, PII S002751070500151X, The Utility of Genetically Altered Mouse Models for Cancer Research
    • Sharpless NE. INK4a/ARF: a multifunctional tumor suppressor locus. Mutat Res. 2005;576(1-2): 22-38. (Pubitemid 40982680)
    • (2005) Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis , vol.576 , Issue.1-2 , pp. 22-38
    • Sharpless, N.E.1
  • 15
    • 30044438229 scopus 로고    scopus 로고
    • WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53
    • DOI 10.1074/jbc.M505590200
    • Chang NS, Doherty J, Ensign A, Schultz L, Hsu LJ, Hong Q. WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53. J Biol Chem. 2005; 280(52):43100-43108. (Pubitemid 43049276)
    • (2005) Journal of Biological Chemistry , vol.280 , Issue.52 , pp. 43100-43108
    • Chang, N.-S.1    Doherty, J.2    Ensign, A.3    Schultz, L.4    Hsu, L.-J.5    Hong, Q.6
  • 16
    • 59149091699 scopus 로고    scopus 로고
    • Identification of ANKRD11 as a p53 coactivator
    • Neilsen PM, Cheney KM, Li CW, et al. Identification of ANKRD11 as a p53 coactivator. J Cell Sci. 2008;121(Pt 21):3541-3552.
    • (2008) J Cell Sci , vol.121 , Issue.PART 21 , pp. 3541-3552
    • Neilsen, P.M.1    Cheney, K.M.2    Li, C.W.3
  • 18
    • 0028071555 scopus 로고
    • Mutations in the p53 tumor suppressor gene: Clues to cancer etiology and molecular pathogenesis
    • Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994;54(18):4855-4878. (Pubitemid 24289415)
    • (1994) Cancer Research , vol.54 , Issue.18 , pp. 4855-4878
    • Greenblatt, M.S.1    Bennett, W.P.2    Hollstein, M.3    Harris, C.C.4
  • 19
    • 0035127864 scopus 로고    scopus 로고
    • Expression of p53 protein in T- and natural killer-cell lymphomas is associated with some clinicopathologic entities but rarely related to p53 mutations
    • DOI 10.1053/hupa.2001.21569
    • Petit B, Leroy K, Kanavaros P, et al. Expression of p53 protein in T- and natural killer-cell lymphomas is associated with some clinicopathologic entities but rarely related to p53 mutations. Hum Pathol. 2001;32(2):196-204. (Pubitemid 32193718)
    • (2001) Human Pathology , vol.32 , Issue.2 , pp. 196-204
    • Petit, B.1    Leroy, K.2    Kanavaros, P.3    Boulland, M.-L.4    Druet-Cabanac, M.5    Haioun, C.6    Bordessoule, D.7    Gaulard, P.8
  • 20
    • 26944461685 scopus 로고    scopus 로고
    • p53 gene mutations are uncommon but p53 is commonly expressed in anaplastic large-cell lymphoma
    • DOI 10.1038/sj.leu.2403840, PII 2403840
    • Rassidakis GZ, Thomaides A, Wang S, et al. p53 gene mutations are uncommon but p53 is commonly expressed in anaplastic large-cell lymphoma. Leukemia. 2005;19(9):1663-1669. (Pubitemid 43090413)
    • (2005) Leukemia , vol.19 , Issue.9 , pp. 1663-1669
    • Rassidakis, G.Z.1    Thomaides, A.2    Wang, S.3    Jiang, Y.4    Fourtouna, A.5    Lai, R.6    Medeiros, L.J.7
  • 21
    • 0028277935 scopus 로고
    • Post-thymic T cell lymphomas frequently overexpress p53 protein but infrequently exhibit p53 gene mutations
    • Matsushima AY, Cesarman E, Chadburn A, Knowles DM. Post-thymic T cell lymphomas frequently overexpress p53 protein but infrequently exhibit p53 gene mutations. Am J Pathol. 1994; 144(3):573-584. (Pubitemid 24176763)
    • (1994) American Journal of Pathology , vol.144 , Issue.3 , pp. 573-584
    • Matsushima, A.Y.1    Cesarman, E.2    Chadburn, A.3    Knowles, D.M.4
  • 23
    • 34248166978 scopus 로고    scopus 로고
    • The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers
    • DOI 10.1172/JCI30866
    • Leong CO, Vidnovic N, DeYoung MP, Sgroi D, Ellisen LW. The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers. J Clin Invest. 2007;117(5):1370-1380. (Pubitemid 46718425)
    • (2007) Journal of Clinical Investigation , vol.117 , Issue.5 , pp. 1370-1380
    • Leong, C.-O.1    Vidnovic, N.2    DeYoung, M.P.3    Sgroi, D.4    Ellisen, L.W.5
  • 24
    • 30344450404 scopus 로고    scopus 로고
    • p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis
    • DOI 10.1016/j.ccr.2005.12.013, PII S1535610805003946
    • Rocco JW, Leong CO, Kuperwasser N, DeYoung MP, Ellisen LW. p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis. Cancer Cell. 2006; 9(1):45-56. (Pubitemid 43069510)
    • (2006) Cancer Cell , vol.9 , Issue.1 , pp. 45-56
    • Rocco, J.W.1    Leong, C.-O.2    Kuperwasser, N.3    DeYoung, M.P.4    Ellisen, L.W.5
  • 26
    • 33750378033 scopus 로고    scopus 로고
    • Tumor-specific p73 up-regulation mediates p63 dependence in squamous cell carcinoma
    • DOI 10.1158/0008-5472.CAN-06-1619
    • DeYoung MP, Johannessen CM, Leong CO, Faquin W, Rocco JW, Ellisen LW. Tumor-specific p73 up-regulation mediates p63 dependence in squamous cell carcinoma. Cancer Res. 2006; 66(19):9362-9368. (Pubitemid 44623630)
    • (2006) Cancer Research , vol.66 , Issue.19 , pp. 9362-9368
    • DeYoung, M.P.1    Johannessen, C.M.2    Leong, C.-O.3    Faquin, W.4    Rocco, J.W.5    Ellisen, L.W.6
  • 27
    • 53049094623 scopus 로고    scopus 로고
    • Therapeutic prospects for p73 and p63: Rising from the shadow of p53
    • Vilgelm A, El-Rifai W, Zaika A. Therapeutic prospects for p73 and p63: rising from the shadow of p53. Drug Resist Updat. 2008;11(4-5):152-163.
    • (2008) Drug Resist Updat , vol.11 , Issue.4-5 , pp. 152-163
    • Vilgelm, A.1    El-Rifai, W.2    Zaika, A.3
  • 28
    • 77958558613 scopus 로고    scopus 로고
    • TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs
    • Su X, Chakravarti D, Cho MS, et al. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature. 2010;467(7318): 986-990.
    • (2010) Nature , vol.467 , Issue.7318 , pp. 986-990
    • Su, X.1    Chakravarti, D.2    Cho, M.S.3
  • 29
    • 73349088166 scopus 로고    scopus 로고
    • TAp63 induces senescence and suppresses tumorigenesis in vivo
    • Guo X, Keyes WM, Papazoglu C, et al. TAp63 induces senescence and suppresses tumorigenesis in vivo. Nat Cell Biol. 2009;11(12):1451-1457.
    • (2009) Nat Cell Biol , vol.11 , Issue.12 , pp. 1451-1457
    • Guo, X.1    Keyes, W.M.2    Papazoglu, C.3
  • 31
    • 60849130706 scopus 로고    scopus 로고
    • Overexpression of delta Np63 in a human nasopharyngeal carcinoma cell line downregulates CKIs and enhances cell proliferation
    • Chiang CT, Chu WK, Chow SE, Chen JK. Overexpression of delta Np63 in a human nasopharyngeal carcinoma cell line downregulates CKIs and enhances cell proliferation. J Cell Physiol. 2009;219(1):117-122.
    • (2009) J Cell Physiol , vol.219 , Issue.1 , pp. 117-122
    • Chiang, C.T.1    Chu, W.K.2    Chow, S.E.3    Chen, J.K.4
  • 32
    • 0034576495 scopus 로고    scopus 로고
    • P63 and P73: P53 mimics, menaces and more
    • Yang A, McKeon F. P63 and P73: P53 mimics, menaces and more. Nat Rev Mol Cell Biol. 2000; 1(3):199-207.
    • (2000) Nat Rev Mol Cell Biol , vol.1 , Issue.3 , pp. 199-207
    • Yang, A.1    McKeon, F.2
  • 33
    • 0034644195 scopus 로고    scopus 로고
    • High level expression of ΔN-p63: A mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?
    • Crook T, Nicholls JM, Brooks L, O'Nions J, Allday MJ. High level expression of deltaN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)? Oncogene. 2000;19(30):3439- 3444. (Pubitemid 30479339)
    • (2000) Oncogene , vol.19 , Issue.30 , pp. 3439-3444
    • Crook, T.1    Nicholls, J.M.2    Brooks, L.3    O'Nions, J.4    Allday, M.J.5
  • 34
    • 77952743819 scopus 로고    scopus 로고
    • Dominant negative (DeltaN) p63alpha induces drug resistance in hepatocellular carcinoma by interference with apoptosis signaling pathways
    • Mundt HM, Stremmel W, Melino G, Krammer PH, Schilling T, Muller M. Dominant negative (DeltaN) p63alpha induces drug resistance in hepatocellular carcinoma by interference with apoptosis signaling pathways. Biochem Biophys Res Commun. 2010;396(2):335-341.
    • (2010) Biochem Biophys Res Commun , vol.396 , Issue.2 , pp. 335-341
    • Mundt, H.M.1    Stremmel, W.2    Melino, G.3    Krammer, P.H.4    Schilling, T.5    Muller, M.6
  • 35
    • 33847009873 scopus 로고    scopus 로고
    • p63 transcriptional regulation of epithelial integrity and cancer
    • Trink B, Osada M, Ratovitski E, Sidransky D. p63 transcriptional regulation of epithelial integrity and cancer. Cell Cycle. 2007;6(3):240-245.
    • (2007) Cell Cycle , vol.6 , Issue.3 , pp. 240-245
    • Trink, B.1    Osada, M.2    Ratovitski, E.3    Sidransky, D.4
  • 37
    • 77950686162 scopus 로고    scopus 로고
    • Identification of DeltaNp63alpha protein interactions by mass spectrometry
    • Amoresano A, Di Costanzo A, Leo G, et al. Identification of DeltaNp63alpha protein interactions by mass spectrometry. J Proteome Res. 2010;9(4): 2042-2048.
    • (2010) J Proteome Res , vol.9 , Issue.4 , pp. 2042-2048
    • Amoresano, A.1    Di Costanzo, A.2    Leo, G.3
  • 38
    • 79959286263 scopus 로고    scopus 로고
    • DeltaNp63 regulates stem cell dynamics in the mammalian olfactory epithelium
    • Packard A, Schnittke N, Romano RA, Sinha S, Schwob JE. DeltaNp63 regulates stem cell dynamics in the mammalian olfactory epithelium. J Neurosci. 2011;31(24):8748-8759.
    • (2011) J Neurosci , vol.31 , Issue.24 , pp. 8748-8759
    • Packard, A.1    Schnittke, N.2    Romano, R.A.3    Sinha, S.4    Schwob, J.E.5
  • 39
    • 79953749348 scopus 로고    scopus 로고
    • The role of p63 in cancer, stem cells and cancer stem cells
    • Nekulova M, Holcakova J, Coates P, Vojtesek B. The role of p63 in cancer, stem cells and cancer stem cells. Cell Mol Biol Lett. 2011;16(2):296-327.
    • (2011) Cell Mol Biol Lett , vol.16 , Issue.2 , pp. 296-327
    • Nekulova, M.1    Holcakova, J.2    Coates, P.3    Vojtesek, B.4
  • 40
    • 67650472752 scopus 로고    scopus 로고
    • The significance of TP53 in lymphoid malignancies: Mutation prevalence, regulation, prognostic impact and potential as a therapeutic target
    • Cheung KJ, Horsman DE, Gascoyne RD. The significance of TP53 in lymphoid malignancies: mutation prevalence, regulation, prognostic impact and potential as a therapeutic target. Br J Haematol. 2009;146(3):257-269.
    • (2009) Br J Haematol , vol.146 , Issue.3 , pp. 257-269
    • Cheung, K.J.1    Horsman, D.E.2    Gascoyne, R.D.3
  • 41
    • 84861495531 scopus 로고    scopus 로고
    • TBL1XR1/TP63: A novel recurrent gene fusion in B-cell non-Hodgkin lymphoma
    • Scott DW, Mungall KL, Ben-Neriah S, et al. TBL1XR1/TP63: a novel recurrent gene fusion in B-cell non-Hodgkin lymphoma. Blood. 2012; 119(21):4949-4952.
    • (2012) Blood , vol.119 , Issue.21 , pp. 4949-4952
    • Scott, D.W.1    Mungall, K.L.2    Ben-Neriah, S.3
  • 42
    • 0032523043 scopus 로고    scopus 로고
    • p16(INK4a) gene inactivation by deletions, mutations, and hypermethylation is associated with transformed and aggressive variants of non-Hodgkin's lymphomas
    • Pinyol M, Cobo F, Bea S, et al. p16(INK4a) gene inactivation by deletions, mutations, and hypermethylation is associated with transformed and aggressive variants of non-Hodgkin's lymphomas. Blood. 1998;91(8):2977-2984. (Pubitemid 28227549)
    • (1998) Blood , vol.91 , Issue.8 , pp. 2977-2984
    • Pinyol, M.1    Cobo, F.2    Bea, S.3    Jares, P.4    Nayach, I.5    Fernandez, P.L.6    Montserrat, E.7    Cardesa, A.8    Campo, E.9
  • 43
    • 77950517259 scopus 로고    scopus 로고
    • CDKN2A-CDKN2B deletion defines an aggressive subset of cutaneous T-cell lymphoma
    • Laharanne E, Chevret E, Idrissi Y, et al. CDKN2A-CDKN2B deletion defines an aggressive subset of cutaneous T-cell lymphoma. Mod Pathol. 2010; 23(4):547-558.
    • (2010) Mod Pathol , vol.23 , Issue.4 , pp. 547-558
    • Laharanne, E.1    Chevret, E.2    Idrissi, Y.3
  • 45
    • 84861971104 scopus 로고    scopus 로고
    • Mutant p53 drives multinucleation and invasion through a process that is suppressed by ANKRD11
    • Noll JE, Jeffery J, Al-Ejeh F, et al. Mutant p53 drives multinucleation and invasion through a process that is suppressed by ANKRD11. Oncogene. 2012;31(23):2836-2848.
    • (2012) Oncogene , vol.31 , Issue.23 , pp. 2836-2848
    • Noll, J.E.1    Jeffery, J.2    Al-Ejeh, F.3
  • 47
    • 78650282006 scopus 로고    scopus 로고
    • Primary cutaneous CD30+ anaplastic large-cell lymphomas show a heterogeneous genomic profile: An oligonucleotide arrayCGH approach
    • Sanchez-Schmidt JM, Salgado R, Servitje O, et al. Primary cutaneous CD30+ anaplastic large-cell lymphomas show a heterogeneous genomic profile: an oligonucleotide arrayCGH approach. J Invest Dermatol. 2011;131(1):269-271.
    • (2011) J Invest Dermatol , vol.131 , Issue.1 , pp. 269-271
    • Sanchez-Schmidt, J.M.1    Salgado, R.2    Servitje, O.3
  • 48
    • 77957555168 scopus 로고    scopus 로고
    • Synergistic chemosensitivity of triple-negative breast cancer cell lines to poly(ADP-Ribose) polymerase inhibition, gemcitabine, and cisplatin
    • Hastak K, Alli E, Ford JM. Synergistic chemosensitivity of triple-negative breast cancer cell lines to poly(ADP-Ribose) polymerase inhibition, gemcitabine, and cisplatin. Cancer Res. 2010;70(20): 7970-7980.
    • (2010) Cancer Res , vol.70 , Issue.20 , pp. 7970-7980
    • Hastak, K.1    Alli, E.2    Ford, J.M.3


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.