RT Journal Article
SR Electronic
T1 Heterogeneous point mutations of the p53 gene in pulmonary fibrosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1404
OP 1408
DO 10.1183/09031936.98.12061404
VO 12
IS 6
A1 S Hojo
A1 J Fujita
A1 I Yamadori
A1 T Kamei
A1 T Yoshinouchi
A1 Y Ohtsuki
A1 H Okada
A1 S Bandoh
A1 Y Yamaji
A1 J Takahara
A1 T Fukui
A1 M Kinoshita
YR 1998
UL http://erj.ersjournals.com/content/12/6/1404.abstract
AB Lung cancer is a frequent complication in pulmonary fibrosis. Overexpression of p53 proteins has been demonstrated by immunostaining in bronchoepithelial cells in patients with idiopathic pulmonary fibrosis. However, it is still unclear whether this overexpressed p53 protein is wild-type or mutant. It was hypothesized that pulmonary fibrosis may be a precancerous lesion with deoxyribonucleic acid point mutations in bronchoepithelial cells. Mutations of the p53 gene were tested for by fluorescence-based single-strand conformation polymorphism (FSSCP), cloning-sequencing and immunostaining techniques. Out of 10 tissue samples that demonstrated overexpression of p53 protein by immunostaining, nine (90%) exhibited point mutations and eight (80%) exhibited heterogeneous point mutations of the p53 gene. The mutations found in pulmonary fibrosis were scattered throughout the central part of the p53 gene, 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 several types of deoxyribonucleic acid damage that occurred in bronchoepithelial cells and this may explain previous findings of a very high incidence of lung cancer complicating pulmonary fibrosis.