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

We analyzed 57 p53 gene mutations in 181 colorectal cancer patients in Taiw an and compiled data on 475 independent p53 mutations in 1,156 primary colo rectal cancer patients worldwide between 1992 to 1998, Transitions at the C pG sites were observed in 31 (54%) and 232 cases (49%), respectively. Frame shift mutations occurring within exons were observed in II (20%) and 50 cas es(10%), respectively, Among the various populations studied, colorectal ca ncer in Taiwan had the lowest p53 mutation rate (31%), highest frequency (2 0%) of frameshift mutations and the second lowest rate (13%) of transversio n mutation. Based on their relation to the base runs, the 61 frameshift mut ations 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 residue s. The p53 frameshift mutational spectrum found in the cases in Taiwan, wit h respect to hotspot sequence, was significantly different from those in th e selected database (p = 0,008), These data support that the patterns of hi gh frequency of transitions at CpG sites and low frequency of transversions in base substitutions in the p53 gene are similar regardless of patient or igin, However, these data also illustrate that frameshift mutations in the p53 gene in colorectal cancer patients are sequence dependent and are disti nct among populations. (C) 2001 Wiley-Liss, Inc.