A detailed study of p53 mutations in colorectal cancer in Singapore

The p53 tumour suppressor gene plays a pivotal role in colorectal cancer formation. Understanding the mechanisms by which p53 is altered in tumour cells could lead to a better understanding of this common cancer. Unfortunately, there is no published information on Chinese patients. We have therefore conducted a series of studies on the p53 tumour suppressor gene in Singaporean colorectal cancer patients and have since demonstrated that 69% of patients have lost one copy of the p53 gene by allelic deletion of chromosome 17p, 55% of patients have a point mutation in one copy of the p53 gene, and that these changes are associated with tumour site, DNA aneuploidy and the pattern of disease dissemination. We present here a further study conducted on the specific nature and frequency of p53 mutations. DNA sequence analysis of 38 tumours from Chinese colorectal cancer patients with p53 mutations showed that 97% (37/38) of the mutations consisted of base substitutions, leading to the incorporation of alternate amino-acids in the p53 protein. The remaining mutation consisted of a single base insertion leading to the generation of a stop-codon, leading to the truncation of the protein some 14 amino-acids downstream from the site of the mutation. Sixty-eight percent of the mutants consisted of guanine to adenine (G-->A) transitions and 58% occurred at CpG dinucleotides. Eighty-seven percent of all mutations occurred at evolutionarily highly conserved regions, with 50% of mutations occurring in codons 175, 248 and 282.(ABSTRACT TRUNCATED AT 250 WORDS)