Gao H G, Chen J K, Stewart J, Song B, Rayappa C, Whong W Z, Ong T
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV 26505-2845, USA.
Carcinogenesis. 1997 Mar;18(3):473-8. doi: 10.1093/carcin/18.3.473.
Studies were performed to examine the mutational pattern of K-ras exons 1 and 2 and p53 exons 5-8 in lung cancer tissues from 27 Chinese patients (10 smokers, 17 non-smokers) using single-stranded conformational polymorphism and DNA sequencing. K-ras mutations were found in 13/27 tumors (48%); all mutations were clustered in exon 1 and distributed between codons 9 and 32. The frequency and number of patients with K-ras mutations between smokers and non-smokers were not different, except that a high frequency of G --> A transitions (11/11) was found in non-smokers. Among cell types, K-ras mutations were found in 7/13 (54%) squamous cell carcinoma (SC) and 5/12 (42%) adenocarcinoma (AC) patients. A --> T transversions (all six transversions) were present only in SC. In p53, 18/27 (67%) tumors contained mutations in exons 7 and 8, frequently at codons 226, 270, 275 and 281. The number of tumors with p53 mutations in smokers (70%) and in non-smokers (65%) was similar, and the mutation frequency did not differ except for a higher number of G --> A (6/7) and T --> C (5/6) transitions in non-smokers. Among cell types, the number of tumors with p53 mutations was 9/13 (69%) in SC and 8/12 (67%) in AC. The A --> G (11/16) transitions and A --> C (4/4) transversions in p53 were more frequent in SC than in AC (P < 0.04 for A --> G; P < 0.02 for A --> C). The varying mutation patterns in both the K-ras and p53 genes between smokers and non-smokers and among cell types suggest that other than cigarette smoke, environmental and dietary factors may also be involved in the genesis of lung cancer among these patients.
开展了多项研究，运用单链构象多态性和DNA测序技术，检测27例中国肺癌患者（10例吸烟者，17例非吸烟者）肺癌组织中K-ras基因第1和第2外显子以及p53基因第5至8外显子的突变模式。在27例肿瘤中有13例（48%）发现K-ras突变；所有突变均聚集在第1外显子，分布于密码子9至32之间。吸烟者与非吸烟者之间K-ras突变患者的频率和数量并无差异，只是在非吸烟者中发现较高频率的G→A转换（11/11）。在细胞类型中，13例鳞状细胞癌（SC）患者中有7例（54%）以及12例腺癌（AC）患者中有5例（42%）发现K-ras突变。A→T颠换（所有6次颠换）仅出现在SC中。在p53基因方面，27例肿瘤中有18例（67%）在第7和第8外显子存在突变，常见于密码子226、270、275和281。吸烟者（70%）和非吸烟者（65%）中发生p53突变的肿瘤数量相似，除了非吸烟者中G→A（6/7）和T→C（5/6）转换数量较多外，突变频率并无差异。在细胞类型中，SC中有9例（69%）肿瘤发生p53突变，AC中有8例（67%）。p53基因中的A→G（11/16）转换和A→C（4/4）颠换在SC中比在AC中更常见（A→G，P<0.04；A→C，P<0.02）。吸烟者与非吸烟者之间以及不同细胞类型中K-ras和p53基因的突变模式各异，这表明除香烟烟雾外，环境和饮食因素可能也参与了这些患者肺癌的发生。
