DISTRIBUTION OF P53 AND K-RAS MUTATIONS IN HUMAN LUNG-CANCER TISSUES

Studies were performed to examine the mutational pattern of K-ras exon s 1 and 2 and p53 exons 5-8 in lung cancer tissues from 27 Chinese pat ients (10 smokers, 17 non-smokers) using single-stranded conformationa l 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-P as mutations between smokers and non-smokers were not different, excep t that a high frequency of G --> A transitions (11/11) was found in no n-smokers, Among cell types, K-ras mutations were found in 7/13 (54%) squamous cell carcinoma (SC) and 5/12 (42%) adenocarcinoma (AC) patien ts, 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, a nd 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 cel l 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 f or A --> G; P < 0.02 for A --> C), The varying mutation patterns in bo th the K-ras and p53 genes between smokers and non-smokers and among c ell types suggest that other than cigarette smoke, environmental and d ietary factors may also be involved in the genesis of lung cancer amon g these patients.