PANCREATIC CARCINOMAS OF ACINAR AND MIXED ACINAR DUCTAL PHENOTYPES INELA-1-MYC TRANSGENIC MICE DO NOT CONTAIN C-K-RAS MUTATIONS/

c-K-ras is activated by mutation at codon 12 in the majority of human pancreatic carcinomas of ductal but not acinar phenotype. The Ela-1-my c transgene when expressed in transgenic mice induces pancreatic carci nomas of both acinar and mixed acinar/ductal phenotype. The histopatho logy of 110 pancreatic carcinomas were characterized in this model. A high percentage of the low to moderately differentiated acinar cell ca rcinomas contain areas of ductal metaplasia. The latter tumors and sev eral well-differentiated acinar tumors were evaluated for c-K-ras muta tion to determine whether there is a relationship between the ductal p henotype and c-K-ras mutation. The polymerase chain reaction and allel e-specific oligomer hybridization were used to determine whether the c -K-ras gene was mutated at codons 12, 13, or 61. Amplified DNA product s from these tumors were also evaluated by single strand conformation polymorphism analysis. Only wild-type c-K-ras was found in these tissu es. Not finding c-K-ras mutation in tumors containing ductal morpholog y indicates that c-K-ras mutation is not a required factor for acinar to ductal metaplasia or a factor in the tumorigenesis of pancreatic tu mors that arise in acinar tissue.