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)
Smith
D R
DR
Department of Colorectal Surgery, Singapore General Hospital.
Chan
C S
CS
Goh
H S
HS
D000782:Aneuploidy; D002681:China / Q000208:ethnology; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D003062:Codon / Q000235:genetics; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012846:Singapore / Q000453:epidemiology
D003062:Codon; D004273:DNA, Neoplasm