메뉴 건너뛰기




Volumn 127, Issue 3, 2011, Pages 853-859

BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer

Author keywords

BRIP1; Germline mutations; Hereditary breast cancer; PALB2; RAD51C

Indexed keywords

ADULT; ARTICLE; BREAST CANCER; BREAST CARCINOGENESIS; CANCER RISK; CAUSAL ATTRIBUTION; CONTROLLED STUDY; DNA REPAIR; DOUBLE STRANDED DNA BREAK; FAMILIAL CANCER; FAMILY HISTORY; FEMALE; GENE BRIP1; GENE PALB2; GENE RAD51C; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HUMAN; MAJOR CLINICAL STUDY; MALE; MISSENSE MUTATION; MUTATIONAL ANALYSIS; NUCLEOTIDE SEQUENCE; OVARY CANCER; PRIORITY JOURNAL; PROGNOSIS; TUMOR GENE; TUMOR SUPPRESSOR GENE;

EID: 79958282990     PISSN: 01676806     EISSN: 15737217     Source Type: Journal    
DOI: 10.1007/s10549-011-1443-0     Document Type: Article
Times cited : (86)

References (52)
  • 1
    • 0015143062 scopus 로고
    • Carcinoma of the breast and ovary in three families
    • 4328854 1:STN:280:DyaE38%2FgslOntg%3D%3D
    • HT Lynch AJ Krush 1971 Carcinoma of the breast and ovary in three families Surg Gynecol Obstet 133 4 644 648 4328854 1:STN:280: DyaE38%2FgslOntg%3D%3D
    • (1971) Surg Gynecol Obstet , vol.133 , Issue.4 , pp. 644-648
    • Lynch, H.T.1    Krush, A.J.2
  • 2
    • 0015524144 scopus 로고
    • Tumor variation in families with breast cancer
    • 4678365 10.1001/jama.222.13.1631 1:STN:280:DyaE3s%2FkvFOrtQ%3D%3D
    • HT Lynch AJ Krush HM Lemon AR Kaplan PT Condit RH Bottomley 1972 Tumor variation in families with breast cancer JAMA 222 13 1631 1635 4678365 10.1001/jama.222.13.1631 1:STN:280:DyaE3s%2FkvFOrtQ%3D%3D
    • (1972) JAMA , vol.222 , Issue.13 , pp. 1631-1635
    • Lynch, H.T.1    Krush, A.J.2    Lemon, H.M.3    Kaplan, A.R.4    Condit, P.T.5    Bottomley, R.H.6
  • 3
    • 0016253104 scopus 로고
    • Familial association of carcinoma of the breast and ovary
    • 4823374 1:STN:280:DyaE2c7ks1Wnsw%3D%3D
    • HT Lynch HA Guirgis S Albert M Brennan J Lynch C Kraft, et al. 1974 Familial association of carcinoma of the breast and ovary Surg Gynecol Obstet 138 5 717 724 4823374 1:STN:280:DyaE2c7ks1Wnsw%3D%3D
    • (1974) Surg Gynecol Obstet , vol.138 , Issue.5 , pp. 717-724
    • Lynch, H.T.1    Guirgis, H.A.2    Albert, S.3    Brennan, M.4    Lynch, J.5    Kraft, C.6
  • 4
    • 46049089154 scopus 로고    scopus 로고
    • National breast and ovarian cancer centre
    • National breast and ovarian cancer centre. Breast Cancer. (2009); http://www.nbocc.org.au/
    • (2009) Breast Cancer
  • 5
    • 79958249795 scopus 로고    scopus 로고
    • National Breast and Ovarian Cancer Centre. National Breast and Ovarian Cancer Centre Surry Hills, NSW
    • National Breast and Ovarian Cancer Centre (2009) Breast cancer risk factors: a review of the evidence. National Breast and Ovarian Cancer Centre, Surry Hills, NSW
    • (2009) Breast Cancer Risk Factors: A Review of the Evidence
  • 6
    • 0037685164 scopus 로고    scopus 로고
    • Breast and ovarian cancer
    • DOI 10.1056/NEJMra012284
    • R Wooster BL Weber 2003 Breast and ovarian cancer NEJM 348 23 2339 2347 12788999 10.1056/NEJMra012284 1:CAS:528:DC%2BD3sXkt1Kktrc%3D (Pubitemid 36638109)
    • (2003) New England Journal of Medicine , vol.348 , Issue.23 , pp. 2339-2347
    • Wooster, R.1    Weber, B.L.2
  • 7
    • 0035030368 scopus 로고    scopus 로고
    • Breast cancer genetics: What we know and what we need
    • DOI 10.1038/87876
    • KL Nathanson R Wooster BL Weber 2001 Breast cancer genetics: what we know and what we need Nat Med 7 5 552 556 11329055 10.1038/87876 1:CAS:528:DC%2BD3MXjsVakurs%3D (Pubitemid 32448321)
    • (2001) Nature Medicine , vol.7 , Issue.5 , pp. 552-556
    • Nathanson, K.N.1    Wooster, R.2    Weber, B.L.3
  • 8
    • 37549056200 scopus 로고    scopus 로고
    • The emerging landscape of breast cancer susceptibility
    • 18163131 10.1038/ng.2007.53 1:CAS:528:DC%2BD1cXhtVyrsQ%3D%3D
    • MR Stratton N Rahman 2008 The emerging landscape of breast cancer susceptibility Nat Genet 40 1 17 22 18163131 10.1038/ng.2007.53 1:CAS:528:DC%2BD1cXhtVyrsQ%3D%3D
    • (2008) Nat Genet , vol.40 , Issue.1 , pp. 17-22
    • Stratton, M.R.1    Rahman, N.2
  • 9
    • 52949096470 scopus 로고    scopus 로고
    • Genetic predisposition to breast cancer: Past, present and future
    • 10.1146/annurev.genom.9.081307.164339 1:CAS:528:DC%2BD1cXht1SnsbbO
    • C Turnbull N Rahman 2008 Genetic predisposition to breast cancer: past, present and future Annu Rev Genom Hum Genet 9 321 345 10.1146/annurev.genom.9. 081307.164339 1:CAS:528:DC%2BD1cXht1SnsbbO
    • (2008) Annu Rev Genom Hum Genet , vol.9 , pp. 321-345
    • Turnbull, C.1    Rahman, N.2
  • 15
    • 62649100810 scopus 로고    scopus 로고
    • Genome-wide linkage scan reveals three putative breast-cancer susceptibility loci
    • 19147119 10.1016/j.ajhg.2008.12.013 1:CAS:528:DC%2BD1MXisFCrt70%3D
    • JM Rosa-Rosa G Pita M Urioste G Llort J Brunet C Lázaro, et al. 2009 Genome-wide linkage scan reveals three putative breast-cancer susceptibility loci Am J Hum Genet 84 2 115 122 19147119 10.1016/j.ajhg.2008.12. 013 1:CAS:528:DC%2BD1MXisFCrt70%3D
    • (2009) Am J Hum Genet , vol.84 , Issue.2 , pp. 115-122
    • Rosa-Rosa, J.M.1    Pita, G.2    Urioste, M.3    Llort, G.4    Brunet, J.5    Lázaro, C.6
  • 16
    • 77952887426 scopus 로고    scopus 로고
    • Genome-wide assocation study identifies five new breast cancer susceptibility loci
    • doi: 10.1038/ng.586
    • Turnbull C, Ahmed S, Morrison J, Pernet D, Renwick A, Maranian M et al. (2010) Genome-wide assocation study identifies five new breast cancer susceptibility loci. Nat Genet. doi: 10.1038/ng.586
    • (2010) Nat Genet
    • Turnbull, C.1    Ahmed, S.2    Morrison, J.3    Pernet, D.4    Renwick, A.5    Maranian, M.6
  • 20
    • 36448950517 scopus 로고    scopus 로고
    • TGFB1 and TGFBR1 polymorphisms and breast cancer risk in the Nurses' Health Study
    • DOI 10.1186/1471-2407-7-175
    • DG Cox K Penney Q Guo SE Hankinson DJ Hunter 2007 TGFB1 and TGFBR1 polymorphisms and breast cancer risk in the Nurses' Health Study BMC Cancer 7 175 175 17848193 10.1186/1471-2407-7-175 (Pubitemid 350162829)
    • (2007) BMC Cancer , vol.7 , pp. 175
    • Cox, D.G.1    Penney, K.2    Guo, Q.3    Hankinson, S.E.4    Hunter, D.J.5
  • 21
    • 77951720395 scopus 로고    scopus 로고
    • Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene
    • 20400964 10.1038/ng.569 1:CAS:528:DC%2BC3cXkvVCjtbo%3D
    • A Meindl H Hellebrand C Wiek V Erven B Wappenschmidt D Niederacher, et al. 2010 Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene Nat Genet 42 5 410 414 20400964 10.1038/ng.569 1:CAS:528:DC%2BC3cXkvVCjtbo%3D
    • (2010) Nat Genet , vol.42 , Issue.5 , pp. 410-414
    • Meindl, A.1    Hellebrand, H.2    Wiek, C.3    Erven, V.4    Wappenschmidt, B.5    Niederacher, D.6
  • 22
    • 77951723100 scopus 로고    scopus 로고
    • Fanconi anemia and breast cancer susceptibility meet again
    • 20428093 10.1038/ng0510-368 1:CAS:528:DC%2BC3cXlt1OlsL0%3D
    • E Levy-Lahad 2010 Fanconi anemia and breast cancer susceptibility meet again Nat Genet 42 5 368 369 20428093 10.1038/ng0510-368 1:CAS:528: DC%2BC3cXlt1OlsL0%3D
    • (2010) Nat Genet , vol.42 , Issue.5 , pp. 368-369
    • Levy-Lahad, E.1
  • 24
    • 78649334861 scopus 로고    scopus 로고
    • FANCJ/BRIP1 recruitment and regulation of FANCD2 in DNA damage responses
    • 20676667 10.1007/s00412-010-0285-6 1:CAS:528:DC%2BC3cXhsVSju7nK
    • F Zhang Q Fan K Ren AD Auerbach PR Andreassen 2010 FANCJ/BRIP1 recruitment and regulation of FANCD2 in DNA damage responses Chromosoma 119 6 637 649 20676667 10.1007/s00412-010-0285-6 1:CAS:528:DC%2BC3cXhsVSju7nK
    • (2010) Chromosoma , vol.119 , Issue.6 , pp. 637-649
    • Zhang, F.1    Fan, Q.2    Ren, K.3    Auerbach, A.D.4    Andreassen, P.R.5
  • 25
    • 33745200945 scopus 로고    scopus 로고
    • Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2
    • 16793542 10.1016/j.molcel.2006.05.022 1:CAS:528:DC%2BD28XmvVCitL8%3D
    • B Xia Q Sheng K Nakanishi A Ohashi J Wu N Christ, et al. 2006 Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2 Mol Cell 22 6 719 729 16793542 10.1016/j.molcel.2006.05.022 1:CAS:528:DC%2BD28XmvVCitL8%3D
    • (2006) Mol Cell , vol.22 , Issue.6 , pp. 719-729
    • Xia, B.1    Sheng, Q.2    Nakanishi, K.3    Ohashi, A.4    Wu, J.5    Christ, N.6
  • 29
    • 77951747926 scopus 로고    scopus 로고
    • Mutation of the RAD51C gene in a Fanconi anemia-like disorder
    • 20400963 10.1038/ng.570 1:CAS:528:DC%2BC3cXkvVCjt7k%3D
    • F Vaz H Hanenberg B Schuster K Barker C Wiek V Erven, et al. 2010 Mutation of the RAD51C gene in a Fanconi anemia-like disorder Nat Genet 42 5 406 409 20400963 10.1038/ng.570 1:CAS:528:DC%2BC3cXkvVCjt7k%3D
    • (2010) Nat Genet , vol.42 , Issue.5 , pp. 406-409
    • Vaz, F.1    Hanenberg, H.2    Schuster, B.3    Barker, K.4    Wiek, C.5    Erven, V.6
  • 31
    • 0142147272 scopus 로고    scopus 로고
    • The BRCT Domain Is a Phospho-Protein Binding Domain
    • DOI 10.1126/science.1088753
    • X Yu CC Chini M He G Mer J Chen 2003 The BRCT domain is a phospho-protein binding domain Science 302 5645 639 642 14576433 10.1126/science.1088753 1:CAS:528:DC%2BD3sXotlWqt7k%3D (Pubitemid 37310919)
    • (2003) Science , vol.302 , Issue.5645 , pp. 639-642
    • Yu, X.1    Chini, C.C.S.2    He, M.3    Mer, G.4    Chen, J.5
  • 33
    • 66349096607 scopus 로고    scopus 로고
    • PALB2 is an integral component of the BRCA complex required for homologous recombination repair
    • 19369211 10.1073/pnas.0811159106 1:CAS:528:DC%2BD1MXlvVyiu7g%3D
    • SM Sy MS Huen J Chen 2009 PALB2 is an integral component of the BRCA complex required for homologous recombination repair Proc Natl Acad Sci USA 106 17 7155 7160 19369211 10.1073/pnas.0811159106 1:CAS:528:DC%2BD1MXlvVyiu7g%3D
    • (2009) Proc Natl Acad Sci USA , vol.106 , Issue.17 , pp. 7155-7160
    • Sy, S.M.1    Huen, M.S.2    Chen, J.3
  • 35
    • 0031472370 scopus 로고    scopus 로고
    • Association of BRCA1 with Rad51 in mitotic and meiotic cells
    • DOI 10.1016/S0092-8674(00)81847-4
    • R Scully J Chen A Plug Y Xiao D Weaver J Feunteun, et al. 1997 Association of BRCA1 with Rad51 in mitotic and meiotic cells Cell 88 2 265 275 9008167 10.1016/S0092-8674(00)81847-4 1:CAS:528:DyaK2sXpsFSnuw%3D%3D (Pubitemid 28015875)
    • (1997) Cell , vol.88 , Issue.2 , pp. 265-275
    • Scully, R.1    Chen, J.2    Plug, A.3    Xiao, Y.4    Weaver, D.5    Feunteun, J.6    Ashley, T.7    Livingston, D.M.8
  • 36
    • 63049108452 scopus 로고    scopus 로고
    • Linking the cellular functions of BRCA genes to cancer pathogenesis and treatment
    • 18954285 10.1146/annurev.pathol.3.121806.151422 1:CAS:528: DC%2BD1MXis1ahsro%3D
    • AR Venkitaraman 2009 Linking the cellular functions of BRCA genes to cancer pathogenesis and treatment Annu Rev Pathol 4 461 487 18954285 10.1146/annurev.pathol.3.121806.151422 1:CAS:528:DC%2BD1MXis1ahsro%3D
    • (2009) Annu Rev Pathol , vol.4 , pp. 461-487
    • Venkitaraman, A.R.1
  • 37
    • 67349222061 scopus 로고    scopus 로고
    • Breast cancer susceptibility: Current knowledge and implications for genetic counselling
    • 19092773 10.1038/ejhg.2008.212 1:CAS:528:DC%2BD1MXmtFKnsLg%3D
    • T Ripperger D Gadzicki A Meindl B Schlegelberger 2009 Breast cancer susceptibility: current knowledge and implications for genetic counselling Eur J Hum Genet 17 6 722 731 19092773 10.1038/ejhg.2008.212 1:CAS:528: DC%2BD1MXmtFKnsLg%3D
    • (2009) Eur J Hum Genet , vol.17 , Issue.6 , pp. 722-731
    • Ripperger, T.1    Gadzicki, D.2    Meindl, A.3    Schlegelberger, B.4
  • 39
    • 10744227178 scopus 로고    scopus 로고
    • Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and BRIP1/BACH1 among BRCA1 and BRCA2-negative probands from breast-ovarian cancer families and among early-onset breast cancer cases and reference individuals
    • DOI 10.1002/humu.10238
    • JL Rutter AM Smith MR Dávila AJ Sigurdson MG Ruthann MA Pineda, et al. 2003 Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and BRIP/BACH1 among BRCA1 and BRCA2-negative probands from breast-ovarian cancer families and among early-onset breast cancer cases and reference individuals Hum Mutat 22 2 121 128 12872252 10.1002/humu.10238 1:CAS:528:DC%2BD3sXms1Cksro%3D (Pubitemid 36950809)
    • (2003) Human Mutation , vol.22 , Issue.2 , pp. 121-128
    • Rutter, J.L.1    Smith, A.M.2    Davila, M.R.3    Sigurdson, A.J.4    Giusti, R.M.5    Pineda, M.A.6    Doody, M.M.7    Tucker, M.A.8    Greene, M.H.9    Zhang, J.10    Struewing, J.P.11
  • 40
    • 68149165614 scopus 로고    scopus 로고
    • Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm
    • 19561590 10.1038/nprot.2009.86 1:CAS:528:DC%2BD1MXovVyns78%3D
    • P Kumar S Henikoff PC Ng 2009 Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm Nat Protoc 4 7 1073 1081 19561590 10.1038/nprot.2009.86 1:CAS:528:DC%2BD1MXovVyns78%3D
    • (2009) Nat Protoc , vol.4 , Issue.7 , pp. 1073-1081
    • Kumar, P.1    Henikoff, S.2    Ng, P.C.3
  • 41
    • 0043122919 scopus 로고    scopus 로고
    • SIFT: Predicting amino acid changes that affect protein function
    • DOI 10.1093/nar/gkg509
    • PC Ng S Henikoff 2003 SIFT: predicting amino acid changes that affect protein function Nucleic Acids Res 31 13 3812 3814 12824425 10.1093/nar/gkg509 1:CAS:528:DC%2BD3sXltVWjs7s%3D (Pubitemid 37442253)
    • (2003) Nucleic Acids Research , vol.31 , Issue.13 , pp. 3812-3814
    • Ng, P.C.1    Henikoff, S.2
  • 43
    • 77951988898 scopus 로고    scopus 로고
    • Pathology of hereditary breast cancer
    • 20436502 10.1038/modpathol.2010.37 1:CAS:528:DC%2BC3cXlsFWjsbs%3D
    • L Da Silva SR Lakhani 2010 Pathology of hereditary breast cancer Mod Pathol 23 Suppl 2 S46 S51 20436502 10.1038/modpathol.2010.37 1:CAS:528:DC%2BC3cXlsFWjsbs%3D
    • (2010) Mod Pathol , vol.23 , Issue.SUPPL. 2
    • Da Silva, L.1    Lakhani, S.R.2
  • 45
    • 77957329128 scopus 로고    scopus 로고
    • PALB2/FANCN: Recombining cancer and Fanconi anemia
    • 20858716 10.1158/0008-5472.CAN-10-1012 1:CAS:528:DC%2BC3cXht1akt7zI
    • M Tischkowitz B Xia 2010 PALB2/FANCN: recombining cancer and Fanconi anemia Cancer Res 70 19 7353 7359 20858716 10.1158/0008-5472.CAN-10-1012 1:CAS:528:DC%2BC3cXht1akt7zI
    • (2010) Cancer Res , vol.70 , Issue.19 , pp. 7353-7359
    • Tischkowitz, M.1    Xia, B.2
  • 46
    • 40349111045 scopus 로고    scopus 로고
    • Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women
    • 10.1186/bcr1828
    • WD Foulkes P Ghadirian MR Akbari N Hamel S Giroux N Sabbaghian, et al. 2007 Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women Breast Cancer Res 9 6 83 10.1186/bcr1828
    • (2007) Breast Cancer Res , vol.9 , Issue.6 , pp. 83
    • Foulkes, W.D.1    Ghadirian, P.2    Akbari, M.R.3    Hamel, N.4    Giroux, S.5    Sabbaghian, N.6
  • 47
    • 69949169651 scopus 로고    scopus 로고
    • Structural basis for recruitment of BRCA2 by PALB2
    • 19609323 10.1038/embor.2009.126 1:CAS:528:DC%2BD1MXoslentbw%3D
    • AW Oliver S Swift CJ Lord A Ashworth LH Pearl 2009 Structural basis for recruitment of BRCA2 by PALB2 EMBO Rep 10 9 990 996 19609323 10.1038/embor.2009.126 1:CAS:528:DC%2BD1MXoslentbw%3D
    • (2009) EMBO Rep , vol.10 , Issue.9 , pp. 990-996
    • Oliver, A.W.1    Swift, S.2    Lord, C.J.3    Ashworth, A.4    Pearl, L.H.5
  • 48
    • 67651166786 scopus 로고    scopus 로고
    • PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and BRCA2
    • 19584259 10.1158/1541-7786.MCR-09-0123 1:CAS:528:DC%2BD1MXos1emtrc%3D
    • F Zhang Q Fan K Ren PR Andreassen 2009 PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and BRCA2 Mol Cancer Res 7 7 1110 1118 19584259 10.1158/1541-7786.MCR-09-0123 1:CAS:528:DC%2BD1MXos1emtrc%3D
    • (2009) Mol Cancer Res , vol.7 , Issue.7 , pp. 1110-1118
    • Zhang, F.1    Fan, Q.2    Ren, K.3    Andreassen, P.R.4
  • 49
    • 62549115236 scopus 로고    scopus 로고
    • PALB2 links BRCA1 and BRCA2 in the DNA-damage response
    • 19268590 10.1016/j.cub.2009.02.018 1:CAS:528:DC%2BD1MXjsFWrtbk%3D
    • F Zhang J Ma J Wu L Ye H Cai B Xia, et al. 2009 PALB2 links BRCA1 and BRCA2 in the DNA-damage response Curr Biol 19 6 524 529 19268590 10.1016/j.cub.2009.02.018 1:CAS:528:DC%2BD1MXjsFWrtbk%3D
    • (2009) Curr Biol , vol.19 , Issue.6 , pp. 524-529
    • Zhang, F.1    Ma, J.2    Wu, J.3    Ye, L.4    Cai, H.5    Xia, B.6
  • 50
    • 77957760669 scopus 로고    scopus 로고
    • Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination
    • 20871615 10.1038/nsmb.1915 1:CAS:528:DC%2BC3cXht1Slur%2FF
    • R Buisson AM Dion-Cote Y Coulombe H Launay H Cai AZ Stasiak, et al. 2010 Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination Nat Struct Mol Biol 17 10 1247 1254 20871615 10.1038/nsmb.1915 1:CAS:528:DC%2BC3cXht1Slur%2FF
    • (2010) Nat Struct Mol Biol , vol.17 , Issue.10 , pp. 1247-1254
    • Buisson, R.1    Dion-Cote, A.M.2    Coulombe, Y.3    Launay, H.4    Cai, H.5    Stasiak, A.Z.6
  • 51
    • 0037130887 scopus 로고    scopus 로고
    • Cancer incidence in BRCA1 mutation carriers
    • D Thompson DF Easton 2002 Cancer incidence in BRCA1 mutation carriers J Natl Cancer Inst 94 18 1358 1365 12237281 1:CAS:528:DC%2BD38Xnt1Gnurs%3D (Pubitemid 35154140)
    • (2002) Journal of the National Cancer Institute , vol.94 , Issue.18 , pp. 1358-1365
    • Thompson, D.1    Easton, D.F.2
  • 52
    • 0033523268 scopus 로고    scopus 로고
    • Cancer risks in BRCA2 mutation carriers
    • The Breast Cancer Linkage Consortium
    • The Breast Cancer Linkage Consortium 1999 Cancer risks in BRCA2 mutation carriers JNCI 91 15 1310 1316
    • (1999) JNCI , vol.91 , Issue.15 , pp. 1310-1316


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.