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Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: results from the ETOP Lungscape Project.
Annals of Oncology ( IF 56.7 ) Pub Date : 2018-01-01 , DOI: 10.1093/annonc/mdx629
K M Kerr 1 , U Dafni 2, 3 , K Schulze 4 , E Thunnissen 5 , L Bubendorf 6 , H Hager 7 , S Finn 8, 9 , W Biernat 10 , L Vliegen 11 , J H Losa 12 , A Marchetti 13 , R Cheney 14 , A Warth 15 , E-J Speel 16 , F Blackhall 17, 18 , K Monkhorst 19 , E Jantus Lewintre 20 , V Tischler 21 , C Clark 22 , J Bertran-Alamillo 23 , P Meldgaard 24 , K Gately 9, 25 , A Wrona 26 , P Vandenberghe 11 , E Felip 27 , G De Luca 13 , S Savic 6 , T Muley 28, 29 , E F Smit 30 , A-M C Dingemans 31 , L Priest 17, 18 , P Baas 32 , C Camps 33, 34, 35 , W Weder 36 , V Polydoropoulou 2 , T R Geiger 37 , R Kammler 37 , T Sumiyoshi 4 , M A Molina 23 , D S Shames 4 , R A Stahel 38 , S Peters 39 ,
Affiliation  

Background Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods Clinically annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is >1% for most of the ∼150 (13 genes) mutations covered in the multiplex test. Results Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63 µg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases. Conclusion Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I-III NSCLC cohort, none of the mutations characterized showed prognostic significance.

中文翻译:

通过多重突变检测NSCLC患者中基因突变的发生率和临床关联性:ETOP Lungscape项目的结果。

背景报道的非小细胞肺癌(NSCLC)中驱动基因突变的发生率是高度可变的,并且临床相关性正在出现。使用来自欧洲胸腔肿瘤平台Lungscape iBiobank的NSCLC生物材料和临床数据,我们探讨了突变的流行病学以及与临床病理特征和患者预后的关联(无复发生存,复发时间,总体生存)。方法使用基于微流体的多重PCR平台评估临床注释,切除的I-III期NSCLC FFPE组织的基因突变。对于多重测试中涵盖的约150个(13个基因)突变中的大多数,突变等位基因检测灵敏度> 1%。结果对2709例Lungscape病例中的2063例(占76.2%)进行了多重检测(中位随访4.8年)。FFPE样品的日期大多是2005年至2008年,但最近提取的DNA的质量和数量总体良好。每例平均DNA产量为2.63 µg;38例(1.4%)QC失败并被排除在研究之外;纳入病例中95.1%允许对完整的突变进行测试。最常见的是KRAS,MET,EGFR和PIK3CA突变,总体患病率分别为23.0%,6.8%,5.4%和4.9%。在鳞癌中,KRAS和EGFR突变在腺癌:PIK3CA中的发生率明显更高。组织学各组之间的MET突变患病率无差异。EGFR突变主要发生在从不吸烟者中。当前/以前吸烟者中的KRAS。对于所有上述突变,在突变和未突变的病例之间结果没有差异。结论FFPE NSCLC档案材料足以进行多重突变分析。在这一大型的,以欧洲为主的临床注释的I-III期NSCLC队列中,所表征的突变均未显示出预后意义。
更新日期:2017-11-23
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