非小细胞肺癌ROS1突变与EGFR突变及临床病理特征的关系
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摘要
目的探讨非小细胞肺癌(NSCLC)中ROS1融合突变与表皮生长因子受体(EGFR)突变及临床病理特征的关系。方法采用实时荧光定量PCR(QPCR)检测2014年12月至2017年12月收治的3487例中国西北地区NSCLC患者ROS1基因的突变情况,同时采用ARMS法检测ROS1基因突变患者的EGFR基因突变情况,分析ROS1和EGFR共突变患者的临床病理特征。结果 3487例NSCLC患者中,ROS1基因突变54例(1. 5%)。ROS1基因突变与年龄、性别、吸烟史、病理类型和临床分期有关(P<0. 05)。54例ROS1融合基因突变患者中有3例(5. 6%)同时存在EGFR基因突变,其中19外显子缺失突变(19-del) 2例,L858R突变1例。3例ROS1突变均为突变体2型(R2)。结论中国西北地区NSCLC患者ROS1融合基因突变率为1. 5%,与EGFR基因突变可以共存。
Objective To investigate the relationship between c-ros oncogene 1( ROS1) fusion gene mutation and epidermal growth factor receptor( EGFR) mutation and clinicopathological characteristics in non-small cell lung cancer( NSCLC). Methods Real-time fluorescence quantitative PCR( QPCR) was performed to examine gene rearrangement of ROS1 fusion gene in 3487 NSCLC patients of Northwest China from December 2014 to December 2017. EGFR mutation was detected by ARMS method for patients with ROS1 fusion gene mutation. The clinicopathological features of patients with double mutations were analyzed. Results Among the 3487 patients,54 patients( 1. 5%) occurred ROS1 fusion gene mutation. ROS1 fusion gene mutation was associated with age,gender,smoking history,pathological types and clinical stage( P<0. 05). Three patients were identified with EGFR mutation from 54 patients who harboring ROS1 fusion genes mutation,including 2 cases of EGFR19 exon deletion mutation( 19-del),and 1 case of EGFR L858 R mutations. The 3 double mutative cases were of ROS1 variant 2( R2). Conclusion ROS1 fusion gene mutative rate of NSCLC patients in Northwest China is 1. 5%. ROS1 fusion gene and EGFR mutations can coexist in NSCLC.
Objective To investigate the relationship between c-ros oncogene 1( ROS1) fusion gene mutation and epidermal growth factor receptor( EGFR) mutation and clinicopathological characteristics in non-small cell lung cancer( NSCLC). Methods Real-time fluorescence quantitative PCR( QPCR) was performed to examine gene rearrangement of ROS1 fusion gene in 3487 NSCLC patients of Northwest China from December 2014 to December 2017. EGFR mutation was detected by ARMS method for patients with ROS1 fusion gene mutation. The clinicopathological features of patients with double mutations were analyzed. Results Among the 3487 patients,54 patients( 1. 5%) occurred ROS1 fusion gene mutation. ROS1 fusion gene mutation was associated with age,gender,smoking history,pathological types and clinical stage( P<0. 05). Three patients were identified with EGFR mutation from 54 patients who harboring ROS1 fusion genes mutation,including 2 cases of EGFR19 exon deletion mutation( 19-del),and 1 case of EGFR L858 R mutations. The 3 double mutative cases were of ROS1 variant 2( R2). Conclusion ROS1 fusion gene mutative rate of NSCLC patients in Northwest China is 1. 5%. ROS1 fusion gene and EGFR mutations can coexist in NSCLC.
引文
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[14] Bubendorf L,Buttner R,Al-Dayel F,et al. Testing for ROS1 in non-small cell lung cancer:a review with recommendations[J].Virchows Arch,2016,469(5):489-503.
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[16] Davies KD, Le AT, Theodoro MF, et al. Identifying and targeting ROS1 gene fusions in non-small cell lung cancer[J].Clin Cancer Res,2012,18(17):4570-4579.
[17] Cai W,Li X,Su C,et al. ROS1 fusions in Chinese patients with non-small-cell lung cancer[J]. Ann Oncol,2013,24(7):1822-1827.
[18] Kim HR,Lim SM,Kim HJ,et al. The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinomas[J]. Ann Oncol,2013,24(9):2364-2370.
[19] Wu S,Wang J,Zhou L,et al. Clinicopathological characteristics and outcomes of ROS1-rearranged patients with lung adenocarcinomas without EGFR,KARS mutations and ALK rearrangements[J]. Thorac Cancer,2015,6(4):413-420.
[20] Mescam-Mancini L,Lantuejoul S,Moro-Sibilot D,et al. On the relevance of a testing algorithm for the detection of ROS1-rearranged lung adenocarcinomas[J]. Lung Cancer,2014,83(2):168-173.
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[22] Mao YJ, Wu SX. ALK and ROS1 concurrent with EGFR mutation in patients with lung adenocarcinoma[J/OL]. Onco Targets Ther,2017[2018-04-20]. https://www. ncbi. nlm. nih.gov/pmc/articles/PMC5513887.
[23] Jessica JL,Lauren LR,Siraj MA,et al. ROS1 fusions rarely overlap with other oncogenic drivers in non-small cell lung cancer[J]. J Thorac Oncol,2017,5(12):872-877.
[2] Siegel RL,Miller KD,Jemal A.Cancer statistics,2015[J]. CA Cancer J Clin,2015,65(1):5-29.
[3] Lynch TJ,Bell DW,Sordella R,et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib[J]. N Engl J Med,2004,350(21):2129-2139.
[4] Fukuoka M,Wu YL,Thongprasert S,et al. Biomarker analyses and final overall survival results from a phaseⅢ,randomized,open-label, first-line study of gefitinb versus carboplatin/paclitaxel in clinically selected patients with advanced non-smallcell lung cancer in Asia(IPASS)[J]. J Clin Oncol,2011,29(21):2866-2874.
[5] Lira ME,Choi YL,Lim SM,et al. A single-tube multiplexed assay for detecting ALK,ROS1,and RET fusions in lung cancer[J]. J Mol Diagn,2014,16(2):229-243.
[6] Go H,Kim DW,Kim D,et al. Clinicopathologic Analysis of the ROS1 rearranged non-small-cell lung cancer and proposal of a diagnostic algorithm[J]. J Thorac Oncol,2013,8(11):1445-1450.
[7] Bergethon K,Shaw AT,Ou SH,et al. ROS1 rearrangements define a unique molecular class of lung cancers[J]. J Clin Oncol,2012,30(8):863-870.
[8] Li C,Fang R,Sun Y,et al. Spectrum of oncogenic driver mutations in lung adenocarcinomas from east asian never smokers[J/OL]. PLoS One,2011[2018-04-20]. https://www. ncbi. nlm.nih.gov/pmc/articles/PMC3227646.
[9] Yoshida T,Oya Y,Tanaka K,et al. Differential crizotinib response duration among ALK fusion variants in ALK-positive nonsmall-cell lung cancer[J]. J Clin Oncol,2016,34(28):3383-3389.
[10] Ettinger DS,Wood DE,Akerley W,et al. NCCN guidelines insights:non-small cell lung cancer,version 4. 2016[J]. J Natl Compr Canc Netw,2016,14(3):255-264.
[11] Zhang XC,Zhang S,Yang XN,et al. Fusion of EML4 and ALK is associates with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression[J/OL]. Mol Cancer,2010[2018-04-15]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908583.
[12] Tiseo M,Gelsomino F,Boggiani D,et al. EGFR and EML4-ALK gene mutations in NSCLC:a case report of erlotinib resistant patient with both concomitant mutations[J]. Lung Cancer,2011,71(2):241-243.
[13] Gainor JF,Shaw AT. Noveltargets in non-small cell lung cancer:ROS1and RET fusions[J]. Oncologist,2013,18(7):865-875.
[14] Bubendorf L,Buttner R,Al-Dayel F,et al. Testing for ROS1 in non-small cell lung cancer:a review with recommendations[J].Virchows Arch,2016,469(5):489-503.
[15] Hirsh FR,Suda K,Wiens J,et al. New and emerging targeted treatments in advanced non-small-cell lung cancer[J]. Lancet,2016,388(10048):1012-1024.
[16] Davies KD, Le AT, Theodoro MF, et al. Identifying and targeting ROS1 gene fusions in non-small cell lung cancer[J].Clin Cancer Res,2012,18(17):4570-4579.
[17] Cai W,Li X,Su C,et al. ROS1 fusions in Chinese patients with non-small-cell lung cancer[J]. Ann Oncol,2013,24(7):1822-1827.
[18] Kim HR,Lim SM,Kim HJ,et al. The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinomas[J]. Ann Oncol,2013,24(9):2364-2370.
[19] Wu S,Wang J,Zhou L,et al. Clinicopathological characteristics and outcomes of ROS1-rearranged patients with lung adenocarcinomas without EGFR,KARS mutations and ALK rearrangements[J]. Thorac Cancer,2015,6(4):413-420.
[20] Mescam-Mancini L,Lantuejoul S,Moro-Sibilot D,et al. On the relevance of a testing algorithm for the detection of ROS1-rearranged lung adenocarcinomas[J]. Lung Cancer,2014,83(2):168-173.
[21] Ju LX,Han MQ,Zhao C,et al. EGFR,KRAS and ROS1 variants coexist in a lung adenocarcinoma patient[J/OL]. Lung Cancer,2016[2018-04-15]. https://www. ncbi. nlm. nih. gov/pubmed/27040858.
[22] Mao YJ, Wu SX. ALK and ROS1 concurrent with EGFR mutation in patients with lung adenocarcinoma[J/OL]. Onco Targets Ther,2017[2018-04-20]. https://www. ncbi. nlm. nih.gov/pmc/articles/PMC5513887.
[23] Jessica JL,Lauren LR,Siraj MA,et al. ROS1 fusions rarely overlap with other oncogenic drivers in non-small cell lung cancer[J]. J Thorac Oncol,2017,5(12):872-877.
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