结直肠癌KRAS、NRAS和BRAF基因罕见突变类型及其临床意义(附1513例)  

Infrequent gene mutations of KRAS,NRAS and BRAF in colorectal cancer and their clinical significance:a report of 1513 cases

作　　者：李艳艳[1] 高静[1] 吉聪聪 章程[1] 李一林[1] 李健 沈琳[1] Li Yanyany;Gao Jing;Ji Congcong;Zhang Cheng;Li Yilin;Li Jian;Shen Lin(Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Gastrointestinal Oncology,Peking University Cancer Hospital&Institute,Beijing 100142,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所消化肿瘤内科,恶性肿瘤发病机制及转化研究教育部重点实验室,100142

出　　处：《中华消化外科杂志》2020年第3期315-323,共9页Chinese Journal of Digestive Surgery

基　　金：国家重点研发计划(2017YFC1309004)。

摘　　要：目的探讨结直肠癌KRAS、NRAS和BRAF基因罕见突变类型及其临床意义。方法采用回顾性描述性研究方法。收集2013年12月至2018年11月北京大学肿瘤医院收治的1513例结直肠癌患者的临床病理资料;男921例,女592例;平均年龄为59岁,年龄范围为15~97岁。提取肿瘤组织基因组DNA,采用Sanger测序法进行KRAS(第2、3外显子),NRAS(第2、3外显子)和BRAF(第15外显子)基因突变检测。观察指标:(1)KRAS、NRAS和BRAF基因突变类型情况。(2)KRAS、NRAS和BRAF基因突变类型与临床病理特征的关系。(3)单一基因罕见突变及其临床病理特征。(4)同时2种基因突变及其临床病理特征。计数资料采用绝对数和百分比表示,组间比较采用χ^2检验。结果(1)KRAS、NRAS和BRAF基因突变类型情况:1513例结直肠癌患者中,KRAS、NRAS和BRAF的基因突变率分别为37.806%(572/1513)、3.173%(48/1513)和5.486%(83/1513)。KRAS外显子2突变率为35.889%(543/1513),外显子3突变率为1.917%(29/1513)。NRAS外显子2突变率为1.322%(20/1513),外显子3突变率为1.851%(28/1513)。BRAF外显子15突变率为5.486%(83/1513)。KRAS基因突变类型主要为外显子2第12、13密码子和外显子3第61密码子突变,突变率分别为27.759%(420/1513)、7.733%(117/1513)和1.586%(24/1513)。7例结直肠癌患者发生KRAS基因第14、59及60密码子区域的罕见突变,突变率为0.463%(7/1513),其中2例[0.132%(2/1513)]V14I突变、2例[0.132%(2/1513)]A59T突变、2例[0.132%(2/1513)]A59E及1例[0.066%(1/1513)]G60D突变。NRAS基因突变类型主要为外显子2第12、13密码子及外显子3第61密码子突变,突变类型主要为Q61K,突变率为0.925%(14/1513),其次为G12D突变,突变率为0.727%(11/1513)。Q61R、Q61H、Q61L、G13R、G12C、G12V、G12S、G13D及G13C的突变率均较低。BRAF基因突变类型主要为外显子15第600密码子突变,突变类型主要为V600E突变,突变率为4.957%(75/1513)。8例结直肠癌患者发生BRAF基因罕见突变,突变Objective To investigate the infrequent gene mutations of KRAS,NRAS and BRAF in colorectal cancer and their clinical significance.Methods The retrospective and descriptive study was conducted.The clinicopathological data of 1513 patients with colorectal cancer who were admitted to the Peking University Cancer Hospital from December 2013 to November 2018 were collected.There were 921 males and 592 females,aged from 15 to 97 years,with an average age of 59 years.The genomic DNA of tumor tissue was extracted,and the mutation status of KRAS(exon 2,3),NRAS(exon 2,3)and BRAF(exon 15)was detected by the Sanger sequencing.Observation indicators:(1)mutation status of KRAS,NRAS and BRAF;(2)relationship of different mutation status of KRAS,NRAS and BRAF with clinicopathological characteristics;(3)infrequent mutation status of single gene and its clinicopathological characteristics;(4)simultaneous mutations of two genes and their clinicopathological characteristics.Count data were expressed by absolute numbers or percentages,and comparison between groups was analyzed by the chi-square test.Results (1)Mutation status of KRAS,NRAS and BRAF:the mutation rates of KRAS,NRAS and BRAF were 37.806%(572/1513),3.173%(48/1513)and 5.486%(83/1513)of the 1513 patients with colorectal cancer,respectively.The mutation rates of exon 2 and exon 3 in KRAS were 35.889%(543/1513)and 1.917%(29/1513),respectively.The mutation rates of exon 2 and exon 3 in NRAS were 1.322%(20/1513)and 1.851%(28/1513),respectively.The mutation rate of exon 15 in BRAF was 5.486%(83/1513).The mutation of KRAS mainly occurred in codon 12,13 of exon 2 and codon 61 of exon 3,with a mutation rate of 27.759%(420/1513),7.733%(117/1513),and 1.586%(24/1513),respectively.Infrequent mutation in codon 14,59,60 of KRAS were found in 7 patients with colorectal cancer[0.463%(7/1513)],including V14I mutation in 2 cases[0.132%(2/1513)],A59T mutation in 2 cases[0.132%(2/1513)],A59E mutation in 2 cases[0.132%(2/1513)]and G60D mutation in 1 case[0.066%(1/1513)].The mutation of NRAS main

关 键 词：结直肠肿瘤 KRAS NRAS BRAF 突变 表皮生长因子受体 

分 类 号：R735[医药卫生—肿瘤]