title: Genetic alterations in p53 and k-ras in lung-cancer in relation to histopathology of the tumor and smoking history of the patient.
abstract: The inactivation of the p53 suppressor gene and the activation of the ras proto-oncogenes are frequent events in non-small cell lung cancer as well as in many other solid neoplasms in man. Somatic mutations in exons 5-8 of the p53 gene were detected in 59% (30/51) of the squamous cell carcinoma and in 38% (14/37) of the adenocarcinoma tumors using GC-clamped, non-radioactive denaturing gradient gel electrophoresis (DGGE). The mutations in the exons 5 and 8 represented larger proportion of the alterations in squamous cell carcinoma tumors (p=0.04; Fisher's exact test, two-tailed); in the adenocarcinoma tumors, mutations were most common in the exon 7 of p53. Most of the identified mutations (25/39; 64%) are predicted to cause an amino acid substitution. Mutations leading to the premature termination of translation were more frequent in adenocarcinoma (6/14) than in squamous cell carcinoma (3/30) tumors (p=0.02). In adenocarcinoma, also base substitutions in the K-ras gene were detected more often (18/37; 49%) than in squamous cell carcinoma (p<0.01). However, a mutation both in p53 and Kras was detected in only 4% of the lung tumors which does not support importance of co-operation between the genes in vivo. Mutations in p53 and K-ras did not correlate with tumor differentiation in either histological type. In squamous cell carcinoma, mutations in p53 showed relation to pack years smoked whereas in adenocarcinoma, mutations in the K-ras gene were associated with cigarette consumption. G to T transversion was the most common type of base substitution in both genes (31% in p53 and 53% in K-ras).
authors.affiliation: INST OCCUPAT HLTH,DEPT OCCUPAT MED,HELSINKI,FINLAND. INST OCCUPAT HLTH,UUSIMAA REG INST,HELSINKI,FINLAND.
authors.forename: M
authors.initials: M
authors.lastname: Ridanpaa
authors.forename: A
authors.initials: A
authors.lastname: Karjalainen
authors.forename: S
authors.initials: S
authors.lastname: Anttila
authors.forename: H
authors.initials: H
authors.lastname: Vainio
authors.forename: K
authors.initials: K
authors.lastname: Husgafvelpursiainen