论文部分内容阅读
目的:了解非小细胞肺癌中PTEN基因突变的分布状况及其临床特征。方法:选取2003年9月至2009年12月间182例在广东省人民医院收治的非小细胞肺癌患者的手术或穿刺标本,抽提RNA后,逆转录成cDNA,再进行PCR扩增PTEN 1～9外显子及EGFR 18～21外显子,用直接测序法检测基因突变。结果:182例标本中,PTEN基因的突变率为9.9%(18/182),PTEN基因的突变率女性为6.5%,男性为11.0%(P=0.549);吸烟者为13.0%,非吸烟者为6.7%(P=0.15);腺癌为7.8%,鳞癌为9.9%(P=0.628),差别均无统计学意义。常见的突变类型有点突变、插入突变及缺失突变,共11例,主要分布在第8外显子,也可见于第4、5、9外显子;其中10例为男性吸烟者,1例为男性非吸烟者;8例为鳞癌,1例腺癌,2例大细胞癌;此外,发现7例大片段缺失突变,缺失片段位于第1～7外显子,约250～539 bp碱基丢失,突变率为3.8%(7/182),除了1例为大细胞癌外,其余6例均为腺癌;PTEN基因突变率与性别、吸烟状态分布无统计学相关性;其中4例大片段缺失伴随EGFR基因敏感突变。结论:具有不同PTEN基因突变类型的NSCLC可能是两种不同的疾病类型,不同突变类型的PTEN基因在NSCLC中的作用机制不同。PTEN基因的大片段缺失可能是突变型EGFR对TKI原发耐药的原因之一。
Objective: To investigate the distribution and clinical features of PTEN gene mutation in non-small cell lung cancer. METHODS: Totally 182 patients with non-small cell lung cancer admitted to Guangdong Provincial People’s Hospital from September 2003 to December 2009 were selected for surgery or puncture. RNA was extracted and reverse transcribed into cDNA for PCR amplification of PTEN 1 ~ 9 exons and exons 18 ~ 21 of EGFR were detected by direct sequencing of gene mutations. Results: The mutation rate of PTEN gene was 9.9% (18/182) in 182 samples. The mutation rate of PTEN gene was 6.5% in women and 11.0% in males (P = 0.549), 13.0% in smokers, non-smoker Was 6.7% (P = 0.15); adenocarcinoma was 7.8%, squamous cell carcinoma was 9.9% (P = 0.628), the difference was not statistically significant. The common mutation types were a bit mutation, insertion mutation and deletion mutation, a total of 11 cases, mainly in the exon 8, also found in exon 4,5,9; of which 10 were male smokers, 1 case was Male non-smoker; 8 cases of squamous cell carcinoma, 1 case of adenocarcinoma, 2 cases of large cell carcinoma; In addition, found seven large deletions, missing fragments located in exons 1 to 7, about 250 ~ 539 bp base , The mutation rate was 3.8% (7/182). Except for 1 case of large cell carcinoma, the other 6 cases were all adenocarcinoma. The mutation rate of PTEN gene had no significant correlation with sex and smoking status. Among them, 4 cases were large Fragment deletion associated with EGFR gene-sensitive mutations. CONCLUSIONS: NSCLCs with different types of PTEN mutations are likely to be two different disease types, and different mutations have different mechanisms of action in NSCLC. Large deletion of PTEN gene may be one of the reasons that the mutant EGFR primary resistance to TKI.