非小细胞肺癌患者肿瘤组织中EGFR和KARS基因突变的分子病理检测分析

目的：探讨非小细胞肺癌患者肿瘤组织中EGFR和KRAS基因各亚型突变情况。方法：应用直接测序方法检测非小细胞肺癌石蜡组织中1273例EGFR基因和1062例KRAS基因突变情况。结果：非小细胞肺癌肿瘤组织中EGFR基因总突变率为36.68%(467/1273)，外显子18、19、20和21的突变率分别为1.02%(13/1273)、18.93%(241/1273)、2.59%(33/1273)和15.95%(203/1273)；EGFR基因各外显子之间双重突变共17例(1.34%)，其中18外显子与20外显子双重突变3例(0.24%)，19外显子与20外显子双重突变7例(0.55%)，19外显子与21外显子双重突变4例(0.31%)和20外显子与21外显子双重突变3例(0.24%)；EGFR基因各外显子内双重突变共2例(2.18%)，均为21外显子双重突变。KRAS基因总突变率为3.01%(32/1062)，外显子2的密码子5、12、13和25的突变率分别为0.09%(1/1062)、2.64%(28/1062)、0.18%(2/1062)和0.09%(1/1062)，外显子3密码子61的突变率为0.09%(1/1062)。结论：非小细胞肺癌患者中EGFR基因存在较高的突变率，尤其为19和21外显子突变，其基因突变亚型分类能指导EGFR-TKI的肿瘤靶向治疗，KRAS基因突变率虽低但不容忽视，其基因突变预示着EGFR-TKI原发耐药。

The molecular pathology detection analysis of EGFR and KRAS gene mutation in non-small cell lung cancer

Objective:To investigate the mutations of each subtype of EGFR gene and KRAS gene in non-small cell lung cancer (NSCLC). Methods:hTe direct sequencing was used to detect the tissues in 1 273 patients of NSCLC with paraffin tissue EGFR gene and 1 062 patients with KRAS gene mutation. Results: The total mutation rate in exons 18 to 21 of EGFR gene was 36.68% (467/1 273) in NSCLC. EGFR gene mutation rate were found in exon 18 (1.02%, 13/1 273), 19 exon (18.93%, 241/1 273), exon 20 (2.59%, 33/1 273) and exon 21 (15.95%, 203/1 273) in the NSCLC. The total double mutation rate between each two exons of EGFR gene was 1.34% (17/1 273). Three cases (0.24%) was identified to have double EGFR gene mutations among exons 18 and 20, exons 20 and 21; 7 cases (0.55%) were identified to have double EGFR gene mutations between exons 19 and 20; 4 cases (0.31%) were identified to have double EGFR gene mutations between exons 19 and 21. The total double mutation in every exon was 0.16% (2/1 273).They both were identified to have double EGFR gene mutations in exons 21. The total mutation rate in KRAS gene was 3.01% (32/1 062) in NSCLC, and mutation rates in 5, 12, 13 and 25 codon of exon 2 were 0.09% (1/1 062), 2.64% (28/1 062), 0.18% (2/1 062) and 0.09% (1/1 062), and 61 codon of exon 3 were 0.09 (1/1 062) in NSCLC tissues. Conclusion: The mutation rate of EGFR gene is high in NSCLC, and these mutations predominantly occur in exons 19 and 21. The subtype mutation can guide the EGFR-TKI target for therapy, and It cannot be ignored that KRAS and BRAF gene mutation rate is low in NSCLC, and the genetic mutation indicates EGFR-TKI primary drug resistance.