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

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 reac...

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Bibliographic Details
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
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Summary: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.
ISSN:0008-5472