K-ras activation in non-small cell lung cancer in the dog

• Published in: Cancer research (Chicago, Ill.) Ill.), 1992-09, Vol.52 (17), p.4724-4727
• Main Authors: Kraegel, S A, Gumerlock, P H, Dungworth, D L, Oreffo, V I, Madewell, B R
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Carcinoma - genetics; Carcinoma - veterinary; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - veterinary; DNA, Neoplasm - genetics; Dogs; Gene Expression Regulation, Neoplastic; Genes, ras; Lung Neoplasms - genetics; Lung Neoplasms - veterinary; Molecular Sequence Data; Mutation; Oligodeoxyribonucleotides - chemistry; Polymerase Chain Reaction; Proto-Oncogene Proteins p21(ras) - genetics; RNA, Messenger - genetics; RNA, Neoplasm - genetics
• ISSN: 0008-5472

To investigate the role of K-ras mutations in canine non-small cell lung cancer, we first determined the nucleotide sequence of the normal canine K-ras gene and then examined 21 canine lung tumors for activating K-ras mutations. Canine K-ras was analyzed by direct sequencing of polymerase chain reaction products generated with oligonucleotide primers derived from the human K-ras sequence. Four nucleotide differences were found between the canine and human K-ras sequence from position 5 to 211. The deduced amino acid sequence of the canine gene was identical to that of the human. Activated K-ras alleles were detected in 5 of the 21 canine lung tumors examined. The activating lesions were point mutations, predominantly in codon 12. Of the 14 adenocarcinomas examined, 2 (14%) had K-ras mutations. Two of 5 (40%) adenosquamous carcinomas and the only large cell carcinoma also contained activated alleles. The overall frequency of K-ras point mutation in non-small cell lung cancer (25%) is similar to that reported in human non-small cell lung cancer. We conclude that K-ras activation by point mutation is associated with, but not necessary for, non-small cell lung cancer development in the dog.