Previously, we observed p53 mutations in the noncancerous tissue that differed from those in lung tumors using the highly sensitive p53 mutation load assay.
Three different patterns in the distribution of p53 mutations in double lung tumours were observed: [A] mutation in only one of the tumours (four cases), [B] different mutations in the tumours (two cases), and [C] same mutation in both tumours (one case).
Lung tumors from 204 smokers with non-small cell lung cancer (NSCLC) were analyzed for mutations in exons 5-8 of the p53 gene and genotypes of XPD and XRCC1. p53 mutations were found in 20% (40/204) of the patients.
Alterations of p53 are one of the most common molecular changes found in all types of lung tumors, suggesting a crucial role for p53 in bronchial carcinogenesis.
The mean in vitro bleomycin-induced breaks per cell (a marker of cancer susceptibility) was significantly higher (0.92) for patients who overexpressed p53 in lung tumour tissue than that for patients with no detectable p53 expression in lung tumour tissue (0.65).
In two cases, the lung tumors exhibited a p53 mutation not present in the previously removed primary tumor and were therefore classified as new primary lung cancers.
There was, in general, an excellent concordance between the lung tumor cell lines and their corresponding tumor tissues for morphology (100%), the presence of aneuploidy (100%), immunohistochemical expression of HER2/neu (100%) and p53 proteins (100%), loss of heterozygosity at 13 chromosomal regions analyzed (97%) using 37 microsatellite markers, microsatellite alterations (MAs, 75%), TP53 (67%), and K-ras (100%) gene mutations.
In conclusion, common genetic variation in TP53 could modulate lung cancer pathways, as suggested by the association with lung cancer in African Americans and somatic TP53 mutation frequency in lung tumors.
Analysis of genetic changes in lung tumors showed that the incidence of mutations in the TP53 and KRAS genes and the incidence of LOH in the FHIT gene were significantly greater in smokers versus non-smokers (P < 0.01).