Distribution of p53 and K-ras mutations in human lung cancer tissues.
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.
Gao
H G
HG
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV 26505-2845, USA.
Chen
J K
JK
Stewart
J
J
Song
B
B
Rayappa
C
C
Whong
W Z
WZ
Ong
T
T
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*
D003062:Codon; D004273:DNA, Neoplasm