非小细胞肺癌表皮生长因子及间变性淋巴瘤激酶基因检测及临床病理特征
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摘要
目的研究汉族人群中表皮生长因子(epidermal growth factor receptor, EGFR)基因突变和间变性淋巴瘤激酶(anaplastic lymphoma kinase, ALK)基因融合在非小细胞肺癌(non-small cell lung cancer, NSCLC)患者中的阳性率及其与临床病理特征的关系。方法收集本院非小细胞肺癌临床手术患者522例,通过ARMS-PCR方法检测NSCLC标本中EGFR基因突变和ALK基因的常见基因融合变异,分析其与患者的病理学分型、性别和年龄等临床指标的相关性。结果对共522例NSCLC手术标本检测了EGFR基因突变,并同时对其中149例标本检测了ALK基因的常见基因融合变异。EGFR基因与ALK融合基因突变阳性率分别为42.91%(224/522)与7.38%(11/149)。EGFR基因突变多发生于女性和腺癌中。另外在149例同时检测了EGFR基因突变和ALK基因融合的标本中,有1例(0.67%,1/149)检测到了EGFR基因突变合并ALK基因融合的罕见驱动基因双突变。结论在汉族人群非小细胞肺癌患者中,EGFR基因突变与患者的性别及病理学分型等临床指标存在明显相关性。ALK基因融合及EGFR、ALK双突变共存型基因突变率虽然较低,但其意义不容忽视,临床医生应给予充分重视。
Objective To explore the mutation frequency of epidermal growth factor receptor(EGFR) gene, anaplastic lymphoma kinase(ALK) fusion gene in Han patients with non-small cell lung cancer(NSCLC) and their relationship with clinical pathological features. Methods The EGFR gene, ALK fusion gene mutation status were detected by real-time quantitative PCR(qRT-PCR) in 522 cases of NSCLC specimens. The correlation with clinical indicators such as pathological type, gender and age of the patient was analyzed. Results EGFR mutation was examined in 522 cases. Among the total sample population, 149 cases were examined for ALK fusion gene. The mutation frequency of EGFR gene, ALK fusion gene were 42.91%(224/522), 7.38%(11/149) respectively. EGFR gene mutations occurred more common in women and adenocarcinoma patients; A double mutation of driving gene was detected from one of the 149 specimens(0.67%, 1/149), a mutation in EGFR gene combined with ALK gene fusion. Conclusion The mutations of EGFR gene in patients with non-small cell lung cancer were associated with the gender and histological type of patients. Mutations in the EGFR gene may coexist with ALK fusion gene mutations in NSCLC specimens, which should be pay attention to by clinician.
Objective To explore the mutation frequency of epidermal growth factor receptor(EGFR) gene, anaplastic lymphoma kinase(ALK) fusion gene in Han patients with non-small cell lung cancer(NSCLC) and their relationship with clinical pathological features. Methods The EGFR gene, ALK fusion gene mutation status were detected by real-time quantitative PCR(qRT-PCR) in 522 cases of NSCLC specimens. The correlation with clinical indicators such as pathological type, gender and age of the patient was analyzed. Results EGFR mutation was examined in 522 cases. Among the total sample population, 149 cases were examined for ALK fusion gene. The mutation frequency of EGFR gene, ALK fusion gene were 42.91%(224/522), 7.38%(11/149) respectively. EGFR gene mutations occurred more common in women and adenocarcinoma patients; A double mutation of driving gene was detected from one of the 149 specimens(0.67%, 1/149), a mutation in EGFR gene combined with ALK gene fusion. Conclusion The mutations of EGFR gene in patients with non-small cell lung cancer were associated with the gender and histological type of patients. Mutations in the EGFR gene may coexist with ALK fusion gene mutations in NSCLC specimens, which should be pay attention to by clinician.
引文
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[5] Vijayvergia N,Mehra R.Clinical challenges in targeting anaplastic lymphoma kinase in advanced non-small cell lung cancer[J].Cancer Chemother Pharmacol,2014,74(3):437-446.
[6] Recondo G,Facchinetti F,Olaussen KA,et al.Making the first move in EGFR-driven or ALK-driven NSCLC:first-generation or next-generation TKI?[J].Nat Rev Clin Oncol,2018,15(11):694-708.
[7] Diaz-Serrano A,Gella P,Jimenez E,et al.Targeting EGFR in lung cancer:Current standards and developments[J].Drugs,2018,78(9):893-911.
[8] Lim SM,Syn NL,Cho BC,et al.Acquired resistance to EGFR targeted therapy in non-small cell lung cancer:Mechanisms and therapeutic strategies[J].Cancer Treat Rev,2018,65:1-10.
[9] Heuckmann JM,Rauh D,Thomas RK.Epidermal growth factor receptor (EGFR) signaling and covalent EGFR inhibition in lung cancer[J].J Clin Oncol,2012,30(27):3417-3420.
[10] Yasuda H,Kobayashi S,Costa DB.EGFR exon 20 insertion mutations in non-small-cell lung cancer:preclinical data and clinical implications[J].Lancet Oncol,2012,13(1):23-31.
[11] Hofman V,Hofman P.Resistances to EGFR tyrosine kinase inhibitors in lung cancer-how to routinely track them in a molecular pathology laboratory?[J].J Thorac Dis,2019,11(Suppl 1):S65-S70.
[12] Zhang YL,Yuan JQ,Wang KF,et al.The prevalence of EGFR mutation in patients with non-small cell lung cancer:a systematic review and meta-analysis[J].Oncotarget,2016,7(48):78985-78993.
[13] Wrona A,Dziadziuszko R,Jassem J.Management of brain metastases in non-small cell lung cancer in the era of tyrosine kinase inhibitors[J].Cancer Treat Rev,2018,71:59-67.
[14] Addeo A,Tabbo F,Robinson T,et al.Precision medicine in ALK rearranged NSCLC:A rapidly evolving scenario[J].Crit Rev Oncol Hematol,2018,122:150-156.
[15] Lin JJ,Riely GJ,Shaw AT.Targeting ALK:Precision medicine takes on drug resistance[J].Cancer Discov,2017,7(2):137-155.
[16] Soda M,Choi YL,Enomoto M,et al.Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer[J].Nature,2007,448(7153):561-566.
[17] Alidousty C,Baar T,Heydt C,et al.Advance of theragnosis biomarkers in lung cancer:from clinical to molecular pathology and biology[J].J Thorac Dis,2019,11(Suppl 1):S3-S8.
[18] Rosas G,Ruiz R,Araujo JM,et al.ALK rearrangements:Biology,detection and opportunities of therapy in non-small cell lung cancer[J].Crit Rev Oncol Hematol,2019,136:48-55.
[19] Kim TJ,Park CK,Yeo CD,et al.Simultaneous diagnostic platform of genotyping EGFR,KRAS,and ALK in 510 Korean patients with non-small-cell lung cancer highlights significantly higher ALK rearrangement rate in advanced stage[J].J Surg Oncol,2014,110(3):245-251.
[20] Le T,Gerber DE.ALK alterations and inhibition in lung cancer[J].Semin Cancer Bio,2017,42:81-88.
[21] Inamura K,Takeuchi K,Togashi Y,et al.EML4-ALK lung cancers are characterized by rare other mutations,a TTF-1 cell lineage,an acinar histology,and young onset[J].Mod Pathol,2009,22(4):508-515.