SYSTEMATIC HRAS AMPLIFICATION IN OVARY-INDEPENDENT MAMMARY-TUMORS - CORRELATION WITH PROGRESSIVELY ANAPLASTIC PHENOTYPES

Progression of well differentiated rat mammary adenocarcinomas to very anaplastic phenotypes was found to correlate with a systematic and si gnificant amplification of a mutant HRAS allele. Tumors with high ampl ification levels of this oncogene were analyzed by chromosomal in situ hybridization; in four of the cases the amplified sequences did not r eside at the native chromosome 1 locus but were localized in a novel m arker chromosome. The model described has potential as a reproducible system for the study of the chromosomal and cellular mechanisms operat ive ''in vivo'' for oncogene amplification.