Analysis of radon-associated squamous cell carcinomas of the lung for a p53 gene hotspot mutation

Squamous cell lung carcinomas (SCC) from former employees of the Wismut ura nium mining company (Saxony, Germany) were obtained from the Stollberg Arch ive in order to screen for p53 tumour suppressor gene codon 249 arg-->met h otspot mutations, a putative molecular bio-dosimeter of alpha-particle (rad on) exposure (Taylor et at (1994) Lancet 343: 86-87; McDonald et al (1995) Cancer Epidemiol Biomarkers Prevent 4: 791-793). Of the 29 archived samples of SCC meeting quality criteria for DNA analysis by polymerase chain react ion (PCR) and Haelll restriction enzyme digestion, two tumours were found t hat harboured this mutation. DNA sequencing confirmed the presence of a G t o T base substitution within the Haelll site spanning codons 249 and 250 of the p53 gene that results in replacement of arginine (wild-type) by methio nine at residue 249. When these data are combined with those from our previ ous study of tumours from the Stollberg Archive in which 50 lung tumours we re examined, (including nine SCCs), we conclude that the G-->T (arg-->met) codon 249 mutation prevalence in the Wismut miner cohort is not sharply ele vated in lung cancers in general (two mutations/79 tumours), or specificall y in SCCs of the lung (two mutations/38 SCC) when compared to data from lun g cancer patients with no reported occupational exposure to radon gas. (C) 2000 Cancer Research Campaign.