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GENETIC ALTERATIONS IN P53 AND K-RAS IN LUNG-CANCER IN RELATION TO HISTOPATHOLOGY OF THE TUMOR AND SMOKING HISTORY OF THE PATIENT

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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).
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Document Type: Research Article

Affiliations: INST OCCUPAT HLTH,DEPT OCCUPAT MED,HELSINKI,FINLAND. INST OCCUPAT HLTH,UUSIMAA REG INST,HELSINKI,FINLAND.

Publication date: November 1, 1994

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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