Document Detail


p53 mutations in L3-loop zinc-binding domain, DNA-ploidy, and S phase fraction are independent prognostic indicators in colorectal cancer: a prospective study with a five-year follow-up.
MedLine Citation:
PMID:  12433709     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
p53 gene alterations are among the most common events observed in colorectal cancer,and are accompanied frequently by DNA aneuploidy and high proliferative activity. The prognostic significance of such mutations remains controversial. We prospectively evaluated the prognostic significance of p53 mutations, DNA-ploidy, and S phase fraction (SPF) in a consecutive series of 160 colorectal cancer patients (median follow-up 71 months). Tumor DNA was screened for p53 mutations by PCR/single-strand conformational polymorphism/sequencing. DNA-ploidy and SPF were assessed by DNA flow cytometry. p53 mutations were detected in 68 of 160 (42.5%) cases. In 56% (38 of 68) of these, p53 mutations were found in conserved areas of the gene and in 44% (30 of 68 cases) outside the conserved regions. Eighteen of the 68 cases (26%) had mutations in the L3 loop, 11 of 68 (16%) in the L1 loop-sheet-alpha helix motif, and 39 of 68 (58%) outside L3 and loop-sheet-alpha helix. Seventy-five percent of the cases (120 of 160) showed DNA aneuploidy, whereas 18% of these (22 of 120) were multiclonal. The major independent predictors for both disease relapse and death were advanced Dukes' stage, p53 mutations affecting L3 loop, DNA-aneuploid tumors, and high SPF (>18.5%). Our results show that mutations in L3 functional domain, more than any mutations, are important biological indicators to predict the outcome of patients indicating that these mutations have biological relevance in terms of colorectal cancer disease course.
Authors:
Antonio Russo; Manuela Migliavacca; Ines Zanna; Maria Rosaria Valerio; Mario Adelfio Latteri; Nello Grassi; Gianni Pantuso; Sergio Salerno; Gabriella Dardanoni; Ida Albanese; Mario La Farina; Rosa Maria Tomasino; Nicola Gebbia; Viviana Bazan
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Publication Detail:
Type:  Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology     Volume:  11     ISSN:  1055-9965     ISO Abbreviation:  Cancer Epidemiol. Biomarkers Prev.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-15     Completed Date:  2003-03-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9200608     Medline TA:  Cancer Epidemiol Biomarkers Prev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1322-31     Citation Subset:  IM    
Affiliation:
Section of Molecular Oncology, Department of Oncology, Regional Reference Center for the Biomolecular Characterization of Neoplasms and Genetic Screening of Hereditary Tumors, Palermo, Italy. Lab-oncobiologia@usa.net
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MeSH Terms
Descriptor/Qualifier:
Aged
Carrier Proteins / diagnostic use*,  genetics*
Codon / genetics
Colorectal Neoplasms / diagnosis*,  genetics*,  mortality
DNA, Neoplasm / diagnostic use*,  genetics*
Exons / genetics
Female
Follow-Up Studies
Genes, p53 / genetics*
Humans
Italy
Male
Middle Aged
Multivariate Analysis
Mutation / genetics
Ploidies
Polymorphism, Genetic / genetics
Prognosis
Prospective Studies
Protein Structure, Tertiary / genetics
S Phase / genetics
Survival Analysis
Tumor Markers, Biological / genetics
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Codon; 0/DNA, Neoplasm; 0/Tumor Markers, Biological; 0/zinc-binding protein

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