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BRAF基因突变在结直肠癌诊治中的研究进展.doc

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BRAF基因突变在结直肠癌诊治中的研究进展.doc
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BRAF V-Raf B1 (v-raf murine sarcoma viral oncogene homolog B, BRAF) - , (mitogen-activated protein kinase, MAPK) , , BRAF ; BRAF ; ; micRNA; , , 2015 , , , , , : 0 (CRC) , , CRC , [1] CRC , , CRC , , CRC , BRAF , , RAS/RAF/MAPK , 1 BRAF MAPK 1983 RAF , RAF , :ARAF, CRAF BRAF ( RAF1) BRAF 7q34 , - , BRAF 90% 15 1799 , 600 , BRAFv600e [2] 10% CRC BRAFV600E, V600E BRAF , BRAF 138 , [3] CRC BRAF , BRAF MAPK , MAPK , , [4] , , (RTK) , , ( RAS-RAF-MEK1/2-ERK1/2) , , , , BRAF V600E , [5] 2 BRAF mic RNA mic RNA 18-25 RNA , 22nt RNA, RNA 3' , / m RNA RNA, CRC :MAPK Wnt , [6] mic RNA CRC [7] Wang [8] BRAF mir-378-5p , CRC BRAF mi R-378-5p , , mi R-378-5p CRC BRAF Nosho [9] mi R-31 CRC BRAF , mi R-31 mi R-21 - , mic RNA [10]; mic RNA, mi R-92a CRC [11], mi R-17-3p mi R-29a [12]; , mi R-17-92 mir-135 [13] mic RNA , BRAF , CRC 3 BRAF 3.1 BRAF , , (CIN) , 80-85% CRC CIN , KRAS BRAF APC P53 , - Cp G (CIMP) , - , BRAFV600E , MLH1 , (MMR) , (MSI) [14] 15-20% CRC MSI , (HNPCC Lynch ) 90% Lynch MSI , 15% MSI, Cp G BRAF (V600E) BRAF MSI-HCRC , , Lynch , MSI, BRAF CRC , Lynch BRAFV600E MLH1 (d MMR) Lynch [15] , , (CMS) :CMS1 (MSIImmune) , , , BRAF , ;CMS2 (Canonical) : , , WNT MYC ;CMS3 (Metabolic) : , ; CMS4 (Mesenchymal) , TGF- , [16] BRAFV600E d MMR CRC ( CMS1) , , 3.2 BRAF BRAF (>60 ) [17], I II 55 BRAF [18] Cremolini BRAF 594 596 BRAFV600E , BRAF 594 596 [19] Jones , 1014 m CRC 137 BRAF , 29 V600E , , BRAFV600E [20] BRAF MSI-H [21-22] BRAFV600E m CRC [23], (PFS) (OS) 2.5 1 [24-25] 4 BRAF , CRC (EGF) (Cetuximab, Panitumumab, ) (VEGF) (bevacizumab, ) BRAF , EGFR , BRAFV600E , EGFR [26] , BRAF BRAF , :I Dabrafenib Vemurafenib Dabrafenib , BRAF ATP , , BRAFV600E II Sorafenib, , BRAF[27] CRAF, VEGFR-1 VEGFR-3 , , BRAF m CRC Vemurafenib EGFR , [28] BGB-283 Raf /EGFR , BRAFV600E EGFR / BGB-283 , MAPK BRAF [29] BRAF encorafenib (LGX818) , RAF , vemurafenib dabarfenib 1b 54 BRAF m CRC , encorafenib encorafenib alpelisib ( ) , encorafenib [30] , BRAF EGFR , P13K MEK1/2 , [31] BRAF [32]: (1) BRAFV600E MAPK ; (2) MAPK ERK DUSP (MAPK ) ; (3) micro RNA , mi R-579-3P BRAF MEK [33] , BRAF BRAF , , BRAF , , 5 BRAFV600E CRC , CRC , CRC , , BRAFV600E , BRAF , CRC , , CRC , [1]Stewart, B.;Wild, C.P. 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[7]Fukushima Y, Iinuma H, Tsukamoto M, et al.Clinical significance of micro RNA- cancer[J].Oncology Reports, 2015, 33 (2) :573. [8]Wang Z, Ma B, Ji X, et al.Micro RNA-378-5p suppresses cell proliferation and induces apoptosis in colorectal cancer cells by targeting BRAF[J].Cancer Cell International, 2015, 15 (1) :40. [9]Nosho K, Igarashi H, Nojima M, et al.Association of micro RNA-31with BRAF mutation, colorectal cancer survival and serrated pathway[J].Carcinogenesis, 2014, 35 (4) :776-83. [10]Schetter AJ, Leung SY, Sohn JJ, et al.Micro RNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma[J].JAMA, 2008, 299:425-436 [] [12]Huang Z, Huang D S, Peng Z, et al.Plasma micro RNAs are promising novel biomarkers for early detection of colorectal cancer[J].International Journal of Cancer, 2010, 127 (1) :118-126. 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