华南地区非小细胞肺癌患者肿瘤组织EGFR,ALK和ROS1基因突变分析
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摘要
目的探讨华南地区非小细胞肺癌(NSCLC)患者肿瘤组织表皮生长因子受体(EGFR),变性淋巴瘤激酶(ALK)和C-ros原癌基因1酪氨酸激酶(ROS1)基因突变特点及其与临床特征的关系。方法收集2016年11月～2017年6月间华南地区76例NSCLC患者肿瘤组织及相应临床资料,利用ARMS法三基因突变联合检测试剂盒检测各肿瘤组织的EGFR,ALK,ROS1基因突变状态,并做各基因突变率与临床特征的相关性分析。结果在华南地区76例NSCLC患者中,EGFR基因突变率为55.3%(42/76),19 del和L858R突变为其主要突变类型,检出1例19del联合L858R共突变;ALK基因融合阳性率为17.1%(13/76),检出4例ALK基因融合联合EGFR基因突变;ROS1基因融合的阳性率为1.3%(1/76),未见ROS1基因联合EGFR基因或ALK基因共突变。与ROS1基因相比,EGFR和ALK基因突变率更高,差异具有统计学意义(χ~2=54.515,P=0.000;χ~2=11.329,P=0.001)。非吸烟NSCLC患者EGFR基因突变率高于吸烟患者,差异具有统计学意义(χ~2=4.578,P=0.032),而ALK与ROS1基因突变率的差异则不具有统计学意义(χ~2=0.000,均P值>0.05);不同年龄、性别和组织学分型的NSCLC患者其EGFR,ALK与ROS1基因突变率的差异不具有统计学意义(χ~2=0.000～2.219,均P值>0.05)。结论 EGFR,ALK和ROS1基因突变均可见于华南地区NSCLC患者,其中以EGFR和ALK基因突变率更高。
Objective To investigate the characteristics of EGFR,ALK and ROS1 mutations in patients with non-small cell lung cancer(NSCLC) in South of China and its relationship with clinical features. Methods The tumor tissues and corresponding clinical data of 76 NSCLC patients in South of China from November 2016 to June 2017 were collected. The mutations of EGFR,ALK and ROS1 were detected by ARMS assay with Joint detection kit. Meanwhile,the correlation between gene mutation rate and clinical features was analyzed. Results The mutation rate of EGFR was 67. 3%(42/76) in 76 patients with NSCLC in South of China,19 del and L858 R mutations were the main mutation types. There was a co-mutation including 19 del and L858 R. The positive rate of ALK gene fusion was 17. 1%(13/76),and 4 cases of ALK gene fusion combined with EGFR mutation were detected. The positive rate of ROS1 gene fusion was 1. 3%(1/76),and there was no co-mutation with other genes. Compared with ROS1,EGFR and ALK mutation rate was higher,the difference was statistically significant(χ~2 =54. 515,P = 0. 000;χ~2 = 11. 329,P=0. 001). The mutation rate of EGFR in non-smoking NSCLC patients was significantly higher than that in smokers(χ~2 =4. 578,P = 0. 032),while the mutation rate of ALK and ROS1 was not statistically significant(χ~2 =0. 000,P>0. 05). There was no statistically significant difference in EGFR, ALK and ROS1 gene mutation rates among NSCLC patients of different age,sex and histology(χ~2 = 0. 000一2. 219,P>0. 05). Conclusion EGFR, ALK and ROS1 gene mutations can be seen in patients with NSCLC in South China,in which EGFR and ALK gene mutation rate is higher.
Objective To investigate the characteristics of EGFR,ALK and ROS1 mutations in patients with non-small cell lung cancer(NSCLC) in South of China and its relationship with clinical features. Methods The tumor tissues and corresponding clinical data of 76 NSCLC patients in South of China from November 2016 to June 2017 were collected. The mutations of EGFR,ALK and ROS1 were detected by ARMS assay with Joint detection kit. Meanwhile,the correlation between gene mutation rate and clinical features was analyzed. Results The mutation rate of EGFR was 67. 3%(42/76) in 76 patients with NSCLC in South of China,19 del and L858 R mutations were the main mutation types. There was a co-mutation including 19 del and L858 R. The positive rate of ALK gene fusion was 17. 1%(13/76),and 4 cases of ALK gene fusion combined with EGFR mutation were detected. The positive rate of ROS1 gene fusion was 1. 3%(1/76),and there was no co-mutation with other genes. Compared with ROS1,EGFR and ALK mutation rate was higher,the difference was statistically significant(χ~2 =54. 515,P = 0. 000;χ~2 = 11. 329,P=0. 001). The mutation rate of EGFR in non-smoking NSCLC patients was significantly higher than that in smokers(χ~2 =4. 578,P = 0. 032),while the mutation rate of ALK and ROS1 was not statistically significant(χ~2 =0. 000,P>0. 05). There was no statistically significant difference in EGFR, ALK and ROS1 gene mutation rates among NSCLC patients of different age,sex and histology(χ~2 = 0. 000一2. 219,P>0. 05). Conclusion EGFR, ALK and ROS1 gene mutations can be seen in patients with NSCLC in South China,in which EGFR and ALK gene mutation rate is higher.
引文
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[17]符萌,冷再君,李传应,等.非小细胞肺癌患者eml4-alk基因检测及eml4-alk阳性患者临床特征分析[J].安徽医科大学学报,2017,52(4):528-533.Fu M,Leng ZJ,Li CY,et al.Detection of eml4-alk fusion gene and analysis of its clinical features in NSCLC patients with eml4-alk fusion gene[J].Acta Universitatis Medicinalis Anhui,2017,52(4):528-533.
[2]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA:A Cancer Journal for Clinicians,2016,66(2):115-132.
[3]Chen Z,Fillmore CM,Hammerman PS,et al.Nonsmall-cell lung cancers:a heterogeneous set of diseases[J].Nature Reviews Cancer,2014,14(8):535-546.
[4]Li T,Kung H,Mack PC,et al.Genotyping and genomic profiling of non-small-cell lung cancer:implications for current and future therapies[J].Journal of Clinical Oncology,2013,31(8):1039-1049.
[5]Matikas A,Kentepozidis N,Georgoulias V,et al.Management of resistance to crizotinib in anaplastic lymphoma kinase-positive non-small-cell lung cancer[J].Clinical Lung Cancer,2016,17(6):474-482.
[6]Juan O,Popat S.Treatment choice in epidermal growth factor receptor mutation-positive non-small cell lung carcinoma:latest evidence and clinical implications[J].Therapeutic Advances in Medical Oncology,2017,9(3):201-216.
[7]Gao J,Aksoy BA,Dogrusoz U,et al.Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal[J].Science Signaling,2013,6(269):p11.
[8]Cerami E,Gao J,Dogrusoz U,et al.The cBio cancer genomics portal:an open platform for exploring multidimensional cancer genomics data[J].Cancer Discovery,2012,2(5):401-404.
[9]周瑞芳,卢仁泉.EGFR基因突变检测的临床应用[J].现代检验医学杂志,2013,28(3):72-74.Zhou RF,Lu RQ.Clinical application of detecting EGFR mutations[J].Journal of Modern Laboratory Medicine,2013,28(3):72-74.
[10]Song A,Kim TM,Kim DW,et al.Molecular changes associated with acquired resistance to crizotinib in ROSl-rearranged non-small cell lung cancer[J].Clinical Cancer Research,2015,21(10):2379-2387.
[11]Mcintyre A,Ganti AK.Lung cancer-A global perspective[J].Journal of Surgical Oncology,2017,115(5):550-554.
[12]Gainor JF,Varghese AM,Ou SH,et al.ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS:an analysis of 1 683 patients with non-small cell lung cancer[J].Clinical Cancer Research,2013,19(15):4273-4281.
[13]Cai W,Li X,Su C,et al.ROS1 fusions in Chinese patients with non-small-cell lung cancer[J].Annals of Oncology,2013,24(7):1822-1827.
[14]Shea M,Costa DB,Rangachari D.Management of advanced non-small cell lung cancers with known mutations or rearrangements:latest evidence and treatment approaches[J].Therapeutic Advances in Respiratory Disease,2016,10(2):113-129.
[15]Lindquist KE,Karlsson A,Leveen P,et al.Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer[J].Oncotarget,2017,8(21):34796-34810.
[16]王京伟,李艳,童永清,等.湖北地区非小细胞肺癌EGFR基因突变及其意义的研究[J].现代检验医学杂志,2016,31(3):7-11,15.Wang JW,Li Y,Tong YQ,et al.Detection of epidermal growth factor receptor(EGFR)mutations and the significance in patients with non-small cell lung cancer(NSCLC)of Hubei province[J].Journal of Modern Laboratory Medicine,2016,31(3):7-11,15.
[17]符萌,冷再君,李传应,等.非小细胞肺癌患者eml4-alk基因检测及eml4-alk阳性患者临床特征分析[J].安徽医科大学学报,2017,52(4):528-533.Fu M,Leng ZJ,Li CY,et al.Detection of eml4-alk fusion gene and analysis of its clinical features in NSCLC patients with eml4-alk fusion gene[J].Acta Universitatis Medicinalis Anhui,2017,52(4):528-533.