Position specificity of Ki-ras oncogene mutations during the progression of colorectal carcinoma.
The Ki-ras proto-oncogene is converted into an active oncogene by mutations in codon 12, 13, or 61. The incidence of mutations in the Ki-ras oncogene in colorectal adenomas and primary colorectal carcinomas has been shown to be 50-75 and 40-65%, respectively. To determine the role activation of the Ki-ras oncogene plays in the progression of colorectal carcinoma, we analyzed DNA from 11 nude-mouse xenografts and from 24 metastases of 22 patients with colorectal carcinoma, using the polymerase chain reaction technique and hybridization with labeled mutation-specific oligomers. Eleven of the 24 metastases (46%) carried mutations, 7 in codon 12 and 4 in codon 13, whereas only 1 nude-mouse tumor (9%) harbored a Ki-ras codon-12 mutation. Eleven of these 12 mutations in advanced stages of colorectal cancer were localized to the second position of either codon 12 or codon 13, whereas a majority of published ras mutations in earlier stages are in the first position of codon 12 of the Ki-ras oncogene. We conclude that there is a position specificity of Ki-ras oncogene mutations in advanced stages of colorectal carcinoma. In general, however, these mutations do not seem to play an important role in the progression of this cancer.
Rochlitz
C F
CF
Department of Hematology/Oncology, Rudolf Virchow Klinikum, Free University of Berlin, FRG.
Heide
I
I
de Kant
E
E
Böhmer
R
R
Peter
F J
FJ
Neuhaus
P
P
Huhn
D
D
Herrmann
R
R
D000595:Amino Acid Sequence; D000818:Animals; D003062:Codon / Q000737:chemistry*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D014183:Transplantation, Heterologous
D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas