Genome wide search for genetic damage in p53 transgenic mouse lung tumours reveals consistent loss of chromosome 4.
The tumour which develops most frequently in mice carrying a p53 Val135 transgene is adenocarcinoma of the lung. We established 10 cell lines from these tumours and investigated their karyotypes by detailed cytogenetic analysis using a complete set of mouse chromosome-specific paints. Consistent loss of chromosome 4 material was noted in 9 out of 10 cell lines; this loss was detected in tetraploid but not diploid cells of the same cell line, suggesting that mouse chromosome 4 plays a critical role in the progression of lung adenocarcinomas. Other frequently observed chromosome aberrations involved chromosomes 7, 5 and 8. Atypical bronchial epithelium was observed together with lung tumours and in tumour-free, apparently normal lungs indicating that mouse lung tumours induced due to the presence of a mutant p53 transgene may develop via pre-invasive lesions and thus may be effective models for the study of lung tumour progression.
Wu
M C
MC
MRC Clinical Oncology & Radiotherapeutics Unit, MRC Centre, Cambridge, U.K.
Sundaresan
M
M
Sundaresan
V
V
Rabbitts
P
P
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D002869:Chromosome Aberrations; D004195:Disease Models, Animal; D016158:Genes, p53; D016678:Genome; D007621:Karyotyping; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D014407:Tumor Cells, Cultured