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 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.
Kraegel
S A
SA
School of Veterinary Medicine, University of California, Davis 95616.
Gumerlock
P H
PH
Dungworth
D L
DL
Oreffo
V I
VI
Madewell
B R
BR
D000818:Animals; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics / Q000662:veterinary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000662:veterinary*; D004273:DNA, Neoplasm / Q000235:genetics; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D008175:Lung Neoplasms / Q000235:genetics / Q000662:veterinary*; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016283:Proto-Oncogene Proteins p21(ras)