Heterogeneous point mutations of the p53 gene in pulmonary fibrosis

Lung cancer is a frequent complication in pulmonary fibrosis, Overexpressio n of p53 proteins has been demonstrated by immunostaining in bronchoepithel ial cells in patients with idiopathic pulmonary fibrosis. However, it is st ill unclear whether this overexpressed p53 protein is wild-type or mutant, It was hypothesized that pulmonary fibrosis may he a precancerous lesion wi th deoxyribonucleic acid point mutations in bronchoepithelial cells. Mutati ons of the p53 gene were tested for by fluorescence-based single-strand con formation polymorphism (FSSCP), cloning-sequencing and immunostaining techn iques, Out of 10 tissue samples that demonstrated overexpression of p53 protein by immunostaining, nine (90%) exhibited point mutations and eight (80%) exhib ited heterogeneous point mutations of the p53 gene. The mutations found in pulmonary fibrosis were scattered throughout the central part of the p53 ge ne, and both guanine (G):cytosine (C) to adenine (A):thymine (T) and A:T to G:C transitions were frequently observed. In conclusion, frequent heterogeneous point mutations of the p53 gene were detected in pulmonary fibrosis, These mutations may have resulted from seve ral types of deoxyribonucleic acid damage that occurred in bronchoepithelia l cells and this may explain previous findings of a very high incidence of lung cancer complicating pulmonary fibrosis.