【摘要】 目的探究转移性结直肠癌患者中KRAS与BRAF基因同时突变类型的治疗及其预后表现。方法纳入114例转移性结直肠癌患者,采用二代测序的方法检测基因,分析KRAS与BRAF基因突变之间的关系;并通过PubMed检索回顾报道转移性结直肠癌患者的文献,进行治疗策略及预后分析。结果 KRAS基因在转移性结直肠癌患者中的突变率为46.49%(53/114):90.57%(48/53)的KRAS基因突变发生在第2外显子,其中以G12D突变最多,占49.06%(26/53)。BRAF基因的突变率为6.14%(7/114),主要为V600E突变,占57.14%(4/7)。KRAS与BRAF基因的突变表现为互斥(P<0.05),但有1例罕见的KRAS与BRAF基因同时突变患者(KRAS第4外显子C351A>C/p.K117N与BRAF第11外显子C1397G>T/p.G466V)。回顾既往文献报道KRAS与BRAF基因同时突变患者共9例,5例选择了手术,其中3例联合化疗。文献中有5例患者报道生存期,结合本次研究报道的1例患者,转移性结直肠癌患者中KRAS与BRAF基因同时突变类型的平均生存时间为(259.00±76.80)d,中位生存期为(180.00±89.41)d。结论转移性结直肠癌患者中,KRAS与BRAF基因突变表现为互斥,但存在小概率的KRAS与BRAF基因同时突变的罕见病例。这一罕见突变类型的相关治疗策略尚无定论,结合回顾既往病例报道的治疗经验,应以手术为主,结合化疗,总体来说预后不佳。更多还原

【Abstract】 Objective To explore the treatment strategy and prognostic performance of concomitant KRAS and BRAF mutation in patients with metastatic colorectal cancer(mCRC). Methods Totally 114 patients with mCRC were enrolled,and the genes were detected by the next-generation sequencing(NGS). The association between KRAS and BRAF mutation was analyzed.The mCRC cases with concomitant KRAS and BRAF mutation reported were collected by searching PubMed,the prognosis and treatment strategies were analyzed. Results The rate of KRAS mutation in mCRC was 46.49%(53/114),90.57%(48/53)of KRAS mutation occurred in exon 2,of which G12 D mutation accounted for 49.06%(26/53).The BRAF mutation rate in mCRC was 6.14%(7/114),mainly V600 E mutation,accounting for 57.14%(4/7).Concomitant KRAS and BRAF mutation was mutually exclusive(P<0.05).However,a case with concomitant KRAS/BRAF mutation in an uncommon mutation site [KRAS exon 4(C351 A>C/p.K117 N) and BRAF exon 11(C1397 G>T/p.G466 V)] was identified.According to previous literature,there were 9 cases of concomitant KRAS and BRAF mutation reported,of which 5 cases chose surgery,and 3 cases received surgery combined with chemotherapy.As only 5 cases reported survival time,combining with the 1 patient in this study,the average overall survival time of mCRC patients with concomitant KRAS and BRAF mutation was(259.00±76.80)days,and the median survival time was(180.00 ± 89.41) days. Conclusion Concomitant KRAS and BRAF mutations in mCRC is very rare,and mostly considered as mutually exclusive.Learning form experience of previous case reports,surgery combines with chemotherapy may be recommended,while the standard treatment strategy is still unclear. The prognosis of this mutation is poor.更多还原