M. Ridanpaa et al., GENETIC ALTERATIONS IN P53 AND K-RAS IN LUNG-CANCER IN RELATION TO HISTOPATHOLOGY OF THE TUMOR AND SMOKING HISTORY OF THE PATIENT, International journal of oncology, 5(5), 1994, pp. 1109-1117
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 (D
GGE). 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 wer
e most common in the exon 7 of p53. Most of the identified mutations (
25/39; 64%) are predicted to cause an amino acid substitution. Mutatio
ns leading to the premature termination of translation were more frequ
ent in adenocarcinoma (6/14) than in squamous cell carcinoma (3/30) tu
mors (p=0.02). In adenocarcinoma, also base substitutions in the K-ras
gene were detected more often (18/37; 49%) than in squamous cell carc
inoma (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 no
t correlate with tumor differentiation in either histological type. In
squamous cell carcinoma, mutations in p53 showed relation to pack yea
rs smoked whereas in adenocarcinoma, mutations in the K-ras gene were
associated with cigarette consumption. G to T transversion was the mos
t common type of base substitution in both genes (31% in p53 and 53% i
n K-ras).