Kraegel S A, Gumerlock P H, Dungworth D L, Oreffo V I, Madewell B R
School of Veterinary Medicine, University of California, Davis 95616.
Cancer Res. 1992 Sep 1;52(17):4724-7.
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.
为了研究K-ras突变在犬非小细胞肺癌中的作用，我们首先测定了正常犬K-ras基因的核苷酸序列，然后检测了21例犬肺肿瘤中是否存在激活的K-ras突变。通过对由源自人类K-ras序列的寡核苷酸引物产生的聚合酶链反应产物进行直接测序来分析犬K-ras。在犬和人类K-ras序列从第5位到211位之间发现了4个核苷酸差异。犬基因推导的氨基酸序列与人类的相同。在所检测的21例犬肺肿瘤中，有5例检测到激活的K-ras等位基因。激活性病变为点突变，主要位于密码子12。在所检测的14例腺癌中，2例（14%）有K-ras突变。5例腺鳞癌中的2例（40%）以及仅有的1例大细胞癌也含有激活的等位基因。非小细胞肺癌中K-ras点突变的总体频率（25%）与人类非小细胞肺癌中报道的频率相似。我们得出结论，点突变导致的K-ras激活与犬非小细胞肺癌的发生有关，但并非其发生所必需。
