title: Mutations and allelic loss of p53 in primary tumor DNA from potentially cured patients with colorectal carcinoma.
abstract: OBJECTIVE
  To compare p53 alterations in survivors and nonsurvivors after surgery for colorectal cancer.
  
  
  METHODS
  Twenty-nine potentially cured patients with colorectal carcinoma, without recurrent disease for more than 6 years after their primary surgery, were selected to match a group of 41 colorectal cancer patients with early metastatic spread to the liver. All patients were screened for mutations in the p53 gene, exons 5 to 9, by denaturing gradient gel electrophoresis and subsequent sequencing.
  
  
  RESULTS
  The frequency of p53 mutations was significantly different in cured patients (60%) compared with patients with early relapse (41%, P <.05). A significant difference was found in the distribution of mutations, indicating that potentially cured patients had a different proportion of mutations in conserved regions of p53 (P =.02). This difference was explained by a significantly different frequency of mutations in exon 8 (40% v 15%, P =.03), which is part of the conserved region V. All mutations in region V were codon 273 mutations in cured patients, whereas three of four mutations were located in codon 273 in patients with metastatic disease. Allelic loss of p53 (loss of heterozygosity [LOH]) was demonstrated in 26% of the cured patients and in 39% of patients with metastatic disease (P =.36). The combination of mutation and LOH of p53 was the same (17%) in both groups.
  
  
  CONCLUSIONS
  A large number of p53 mutations in colorectal cancer do not promote disease progression. Some mutations, particularly within conserved regions, may even counteract negative functional effects of other p53 structural alterations. A complete loss of p53 function was not related to survival or progression after curative operation of colorectal carcinoma.
authors.affiliation: Surgical Metabolic Research Laboratory at the Lundberg Laboratory for Cancer Research, Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Forslund
authors.forename: C
authors.initials: C
authors.lastname: Lönnroth
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.forename: H
authors.initials: H
authors.lastname: Brevinge
authors.forename: K
authors.initials: K
authors.lastname: Lundholm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm