【摘要】：目的分析結(jié)直腸癌(colorectal cancer,CRC)組織中KRAS、NRAS、BRAF和PIK3CA基因的常見突變類型及其與臨床病理指標(biāo)的關(guān)系。方法對(duì)252例CRC石蠟包埋組織進(jìn)行DNA提取,采用Sanger測(cè)序法對(duì)KRAS、NRAS、BRAF和PIK3CA基因進(jìn)行檢測(cè),分析各個(gè)基因的突變率與臨床病理特征的關(guān)系,并統(tǒng)計(jì)各個(gè)基因的突變類型。結(jié)果 252例CRC中,KRAS、BRAF、NRAS和PIK3CA突變發(fā)生率在性別、年齡、腫瘤部位、病理分期和有無淋巴結(jié)轉(zhuǎn)移上差異均無統(tǒng)計(jì)學(xué)意義(P0.05);檢測(cè)陽性突變共140例(55.5%),其中KRAS 113例(44.8%),NRAS 1例(0.4%),BRAF 19例(7.5%),PIK3CA 28例(11.1%),包括PIK3CA與KRAS、NRAS、BRAF基因發(fā)生雙突變21例(8.3%);KRAS的主要突變類型包括G12A、G12C、G12D、G12R、G12S、G12V、G13D、T20M、A59T、Q61H、Q61L、Q61P;NRAS僅有1例突變?yōu)镚12D;BRAF的主要突變類型為V600E、D594G、K601E;PIK3CA的主要突變類型包括E542K、E545K、Q546K、Q546P、Q546R、M1043I、H1047R。PIK3CA與KRAS、NRAS、BRAF之間會(huì)發(fā)生交叉突變,但KRAS、NRAS、BRAF三者之間基本不存在交叉突變。結(jié)論 CRC中KRAS陽性突變率居高,PIK3CA次之,BRAF、NRAS突變率最低,且PIK3CA常與KRAS、NRAS、BRAF發(fā)生交叉突變。對(duì)CRC患者行KRAS、NRAS、BRAF、PIK3CA等多基因檢測(cè),可正確指導(dǎo)并選擇抗EGFR單抗藥,從而實(shí)現(xiàn)真正意義上的個(gè)體化靶向治療。
[Abstract]:Objective to analyze the common mutation types of KRAS,NRAS,BRAF and PIK3CA genes in colorectal cancer (colorectal cancer,CRC) and their relationship with clinicopathological parameters. Methods DNA was extracted from 252 cases of CRC paraffin embedded tissues. The KRAS,NRAS,BRAF and PIK3CA genes were detected by Sanger sequencing. The relationship between the mutation rate of each gene and the clinicopathological characteristics was analyzed, and the mutation types of each gene were analyzed. Results there was no significant difference in the incidence of KRAS,BRAF,NRAS and PIK3CA mutation in sex, age, tumor location, pathological stage and lymph node metastasis in 252 cases of CRC (P0.05). A total of 140 cases (55.5%) were detected positive mutations, including KRAS 113 cases (44.8%), NRAS 1 case (0.4%), BRAF 19 cases (7.5%), PIK3CA 28 cases (11.1%), including PIK3CA and KRAS,NRAS,). There were 21 cases (8.3%) with double mutation of BRAF gene. The main mutation types of KRAS include G12An G12C, G12RG12RG12RG12RG12SU G12VG13DUT T20MU A59T10Q61LQ61PNRAs, only one main mutation type of G12DU BRAF is V600EN D594GUK601E; The main mutation types of PIK3CA include E542KU, E545KGN, Q546K, Q546P, Q546RPIK3CA, M1043IH1047R.PIK3CA and KRAS,NRAS,BRAF, but there is no cross mutation between KRAS,NRAS,BRAF and M1043IH1047R.PIK3CA. Conclusion the positive mutation rate of KRAS is higher in CRC, followed by PIK3CA, BRAF,NRAS mutation is the lowest, and PIK3CA often has cross mutation with KRAS,NRAS,BRAF. The detection of KRAS,NRAS,BRAF,PIK3CA and other polygenes in patients with CRC can correctly guide and select anti EGFR monoclonal resistance, so as to realize individual targeted therapy in real sense.
【作者單位】： 廣東省中醫(yī)院病理科;
【分類號(hào)】：R735.34
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本文編號(hào)：2366655