Progression of squamous carcinoma cells to spindle carcinomas of mouse skin is associated with an imbalance of H-ras alleles on chromosome 7

Analysis of benign and malignant mouse skin tumors had previously shown that amplification of a mutant H- ras allele or loss of the normal allele was 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 histological types. Some tumors had virtually no signal corresponding to the normal allele and 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 experiments on cell lines derived from squamous or spindle cell tumors have demonstrated a good correlation between the ratio of normal:mutant ras and the degree of invasiveness of the cells in in vitro assays.