title: Mutations of the APC gene in human sporadic colorectal cancers.
abstract: BACKGROUND
  Mutations of the APC gene are reported to occur frequently in sporadic colorectal adenomas and adenocarcinomas. We studied APC gene mutations in cases of human sporadic colorectal cancer in order to evaluate their correlation with pathologic characteristics and clinical prognosis.
  
  
  METHODS
  Most of the mutations of the APC gene (95%) are nonsense or frame shift mutations, encoding for truncated APC proteins. For this reason, mutation detection of the APC gene was performed using the in vitro synthesized protein (IVSP) assay, analysing the region between nucleotide 2058 and nucleotide 5079 of the gene, containing the mutation cluster region.
  
  
  RESULTS
  Out of 58 cases of colorectal cancer, 29 presented a mutated form of APC (mutation frequency 50%). We did not find a statistically significant correlation between APC gene mutation and age, sex, localization of the primary tumour, grading, Crohn-like lymphoid reaction or presence of residual adenoma. Tumours with low invasivity (Dukes' stages A and B) were less frequently mutated (12/27, 44.5%) than tumours of Dukes' stage C (15 out of 21, 71.4%), which developed macroscopically secondary metastasis with variable latency after surgery. Highly invasive tumours with synchronous metastases (Dukes' stage D) had, instead, a low frequency of APC mutations (20%, 2/10) (P = 0.02, compared with Dukes' stages A, B and C).
  
  
  CONCLUSIONS
  These data suggest that more aggressive Dukes' stage D tumours develop metastasis by means of an unknown mechanism, independent of APC mutation.
authors.affiliation: Dept of Pharmacology, University of Florence, Italy. cdefilippo@pharm.unifi.it
authors.forename: C
authors.initials: C
authors.lastname: De Filippo
authors.forename: C
authors.initials: C
authors.lastname: Luceri
authors.forename: G
authors.initials: G
authors.lastname: Caderni
authors.forename: M
authors.initials: M
authors.lastname: Pacini
authors.forename: L
authors.initials: L
authors.lastname: Messerini
authors.forename: A
authors.initials: A
authors.lastname: Biggeri
authors.forename: E
authors.initials: E
authors.lastname: Mini
authors.forename: F
authors.initials: F
authors.lastname: Tonelli
authors.forename: F
authors.initials: F
authors.lastname: Cianchi
authors.forename: P
authors.initials: P
authors.lastname: Dolara
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D018389:Codon, Nonsense; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D017491:Genes, APC; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016019:Survival Analysis
chemical_list: D018389:Codon, Nonsense; D004273:DNA, Neoplasm