Progression of Squamous Carcinoma Cells to Spindle Carcinomas of Mouse Skin Is Associated with an Imbalance of ll-ms AlÃ-eleson Chromosome 7'

Analysis of benign and malignant mouse skin tumors had previouslyshown that amplification of a mutant H-ras alÃ-eleor loss of the normal alÃ-elewas generally seen only in high grade or spindle cell tumors. The normal:mutant ras gene dosage has been studied directly by polymerase chain reaction amplification of DNA derived from paraffin sections of carcinomas of defined histolÃ3gica!types. Some tumors had virtually no signal corresponding to the normal alÃ-eleand these were invariably spindle cell carcinomas. In four cases where both squamous and spindle cell components could be identified within the same tumor the spindle cell component had a higher mutant-normal gene ratio. Additional exper iments on cell lines derived from squamous or spindle cell tumors have demonstrated a good correlation between the ratio of normahmutant ras and the degree of invasiveness of the cells in in vitro assays.