Frequency and spectrum of K-RAS codons 12 and 13 mutations in colorectal adenocarcinomas from Taiwan.
Mutations in codons 12 and 13 of the K-RAS oncogene are detected at a remarkably high frequency in colorectal adenocarcinoma and are believed to be a critical event in oncogenesis. In the present study, we evaluated colorectal tumor specimens from Taiwan for mutations in K-RAS codons 12 and 13 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and direct DNA sequencing. Mutations were found in 48 of 181 (26.5%) tumors, 30 mutations were G-->A transitions (62.5% of all mutations), 14 were G-->T transversions (29.2%), and only 4 were G-->C transversions (8.3%). Similar relative mutation frequencies and spectra were found regardless of the sex of the patient, the tumor grade, or the tumor stage. The high frequency of transitions among K-RAS mutation suggests that G/T mismatches play an important role in the oncogenesis of colorectal adenocarcinoma, implying that alkylating carcinogens may be involved in the colorectal carcinogenesis. Although the frequency of mutation (26.5%) appears to be lower than those reported in the United States (40%), France (49%), and the Netherlands (34%), the spectrum of point mutations in codons 12 and 13 of the K-RAS gene in the Taiwan Chinese population appears to be similar. The reason for these results may be that diet and ethnicity are not rate limit factors in controlling the spectra of mutations but influence on the frequency of K-RAS mutations in human colorectal adenocarcinomas.
Wu
Chi-Ming
CM
Graduate Institute of Basic Medical Science, Chang Gung University, Taoyuan 333, Taiwan. chimingwu@adm.cgmh.org.tw
Tang
Reiping
R
Wang
Jeng-Yi
JY
Changchien
Chung-Rong
CR
Hsieh
Ling-Ling
LL
D000230:Adenocarcinoma / Q000235:genetics*; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013624:Taiwan
D003062:Codon