[Evaluation of Consistency in detection of epidermal growth factor receptor gene T790M mutation in plasma and tumor specimens of patients with lung adenocarcinoma].

Publisher: Chinese Medical Association Country of Publication: China NLM ID: 7910681 Publication Model: Print Cited Medium: Print ISSN: 0253-3766 (Print) Linking ISSN: 02533766 NLM ISO Abbreviation: Zhonghua Zhong Liu Za Zhi Subsets: MEDLINE

Publication: Peking : Chinese Medical Association
Original Publication: Beijing, Zhonghua yi xue hui.

Genes, erbB-1* ; Mutation*; Adenocarcinoma/*genetics ; Lung Neoplasms/*genetics; Adenocarcinoma/drug therapy ; Adenocarcinoma of Lung ; Antineoplastic Agents/therapeutic use ; Exons ; Gefitinib ; Healthy Volunteers ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms/drug therapy ; Quinazolines/therapeutic use ; Sensitivity and Specificity

Objective: To evaluate the consistency in detection of T790M mutation of epidermal growth factor receptor gene (EGFR) in plasma and tumor samples of patients with lung adenocarcinoma. Methods: The tumor tissues or cytological specimens of 12 patients with operable lung adenocarcinoma(stage Ⅰ-ⅢA) and 100 patients with advanced stage ⅢB-Ⅳ lung adenocarcinoma were collected, among which 11 patients showed acquired resistance for gefitinib (11/100). In the same period, peripheral blood samples were collected from all patients and 50 healthy volunteers. Amplification refractory mutation system (ARMS) was used to detect EGFR mutations in tumor specimens. Next Generation Sequencing(NGS) based circulating single-molecule amplification and resequencing technology (cSMART)was performed to quantitatively detect the EGFR mutations in circulating tumor DNA (ctDNA) from plasma specimens. Results: The sensitivity, specificity and concordance rate of EGFR T790M mutation between plasma and tissue specimens from 100 advanced stage patients were 50.0%, 72.9% and 72.0%, respectively. For L858R mutation and exon 19 deletion mutations, the above mentioned sensitivity, specificity and concordance rate were 91.7%, 100.0%, and 98.0%, as well as 79.2%, 100.0% and 95.0%, respectively. The L858R mutation and exon 19 deletion mutations were not detected in plasma of 50 healthy volunteers, whereasT790M mutation(1.0±0.0 copies) was found in 7 individuals(7/50, 14.0%). Similarly, in 12 resectable patients, 4 (4/12, 33.3%) T790M mutations were found in plasma (1.2±0.2 copies), but no L858R mutation and 19 exon deletion mutations. In comparison, 28.0% of patients with advanced lung adenocarcinoma (28/100)had detectable T790M mutation in plasma with copy numbers (34.0±22.7 copies). Furthermore, the copy numbers of T790M were 268.2±119.9 in plasma of 5 cases with acquired gefitinib-resistance. Conclusions: In patients with advanced stages of lung adenocarcinoma, the detection of T790M mutation in plasma and tumor specimens is low. The T790M mutation also exists in the plasma of some healthy controls, suggesting that T790M mutation participates in EGFR signaling pathway and it might function in healthy population.

Keywords: Adenocarcinoma; Carcinoma, non-small-cell lung; Point mutation; Receptor, epidermal growth factor; T790M
Local Abstract: [Publisher, Chinese] 目的： 探讨肺腺癌患者血浆和肿瘤标本中表皮生长因子受体(EGFR)基因T790M位点突变检测结果的一致性。 方法： 收集12例可手术切除(Ⅰ～ⅢA期)及100例进展期(ⅢB～Ⅳ期)肺腺癌患者的组织或细胞学肿瘤标本，其中11例标本为吉非替尼获得性耐药患者，并配对采集患者外周血标本。同期获得50例健康志愿者外周血标本。肿瘤标本采用扩增受阻突变系统方法检测EGFR基因突变，配对血浆标本采用二代测序环化单分子扩增和重测序技术检测循环肿瘤DNA EGFR基因突变。 结果： 100例进展期肺腺癌患者血浆和肿瘤标本中，EGFR基因T790M位点突变的敏感度、特异度和一致率分别为50.0%、72.9%和72.0%，L858R位点突变的敏感度、特异度和一致率分别为91.7%、100.0%和98.0%，19外显子缺失突变的敏感度、特异度和一致率分别为79.2%、100.0%和95.0%。50例健康志愿者血浆中T790M突变[(1.0±0.0)拷贝] 7例(14.0%)，未检出L858R突变和19外显子缺失突变。12例可手术切除肺腺癌患者血浆中，T790M突变[(1.2±0.2)拷贝] 4例(33.3%)，未检出L858R和19外显子缺失突变。100例进展期肺腺癌患者血浆中，T790M位点突变28例(28.0%)，拷贝数为(34.0±22.7)拷贝。11例获得性吉非替尼耐药患者血浆中，T790M突变5例，拷贝数为(268.2±119.9)拷贝。 结论： 进展期肺腺癌患者血浆及肿瘤标本中，检测T790M位点的敏感度、特异度和一致率低。健康志愿者血浆中存在T790M突变，可能提示T790M位点突变为EGFR信号传导路径的调节者，且在健康人群中具有一定的生理功能。.

0 (Antineoplastic Agents)
0 (Quinazolines)
S65743JHBS (Gefitinib)

Date Created: 20180125 Date Completed: 20180212 Latest Revision: 20190221

20240628

10.3760/cma.j.issn.0253-3766.2018.01.006

29365415