Mutations of p53 gene in human colorectal cancer: distinct frameshifts among populations

We analyzed 57 p53 gene mutations in 181 colorectal cancer patients in Taiwan and compiled data on 475 independent p53 mutations in 1,156 primary colorectal cancer patients worldwide between 1992 to 1998. Transitions at the CpG sites were observed in 31 (54%) and 232 cases (49%), respectively. Frameshift mutations occurring within exons were observed in 11 (20%) and 50 cases (10%), respectively. Among the various populations studied, colorectal cancer in Taiwan had the lowest p53 mutation rate (31%), highest frequency (20%) of frameshift mutations and the second lowest rate (13%) of transversion mutation. Based on their relation to the base runs, the 61 frameshift mutations could be grouped into 4 subclasses. After corrections were made for differences in the base number in a run, the relative mutational frequency at a base run was found to be 9- to 47-fold over that in the no-run residues. The p53 frameshift mutational spectrum found in the cases in Taiwan, with respect to hotspot sequence, was significantly different from those in the selected database (p = 0.008). These data support that the patterns of high frequency of transitions at CpG sites and low frequency of transversions in base substitutions in the p53 gene are similar regardless of patient origin. However, these data also illustrate that frameshift mutations in the p53 gene in colorectal cancer patients are sequence dependent and are distinct among populations.