Document Detail


Detection and possible prognostic relevance of p53 gene mutations in diffuse large B-cell lymphoma. An analysis of 51 cases and review of the literature.
MedLine Citation:
PMID:  15370252     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Although the presence of p53 gene mutations has been considered as a bad prognostic feature in DLBCL, its clinical significance is still controversial. The aims of this study were: detect the presence of mutations in exons 5 to 9 of the p53 gene and correlate it to prognosis in DLBCL. Fifty-one DLBCL patients were enrolled in this study. Expression of p53 was evaluated by immunohistochemistry. The screening of p53 mutations was performed using PCR-SSCP methods. Cases showing a mobility shift on SSCP electrophoresis were analyzed by automatic sequencing. We could identify 8 missense mutations in 6 of 48 cases (12.5%). In addition, we found a known polymorphism at codon 213 and 2 instances of silent mutations. Of all mutations/polymorphisms found, 7 (64%) were localized in codons previously described as p53 hot spots in NHL cases. Of the remaining alterations (4 or 36%), 2 mutations were localized in codons previously described as hot spots for p53 in other tumors and 2 (codon 142 of the exon 5 and codon 195 of the exon 6), in codons not described as hot spots for p53 up to now. The presence of missense mutations in exons 5 to 9 of p53 gene had adverse impact on overall survival (P = 0.020). Cox's Regression Model identified that high-risk International Prognostic Index (IPI) and p53 gene mutations have independent negative impact on OS. Therefore, the association of IPI with cellular factors, such as p53 mutation, can be very helpful in deciding when we should indicate more aggressive therapies in patients with DLBCL, to somehow increase the chance of cure in these patients.
Authors:
Fábio R Kerbauy; Gisele W B Colleoni; Sara T O Saad; Maria Regina Regis Silva; Antonio Correa Alves; Kátia C C Aguiar; Dulcinéia M Albuquerque; Jörg Kobarg; Maria Tereza Seixas; José Kerbauy
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Leukemia & lymphoma     Volume:  45     ISSN:  1042-8194     ISO Abbreviation:  Leuk. Lymphoma     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-16     Completed Date:  2005-04-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9007422     Medline TA:  Leuk Lymphoma     Country:  England    
Other Details:
Languages:  eng     Pagination:  2071-8     Citation Subset:  IM    
Affiliation:
Discipline of Hematology and Hemotherapy--Universidade Federal de São Paulo, UNIFESP/EPM, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Cohort Studies
Exons
Humans
Lymphoma, B-Cell / diagnosis,  genetics,  mortality
Lymphoma, Large B-Cell, Diffuse / diagnosis*,  genetics*,  mortality
Middle Aged
Mutation*
Prognosis
Survival Analysis
Treatment Outcome
Tumor Suppressor Protein p53 / genetics*
Chemical
Reg. No./Substance:
0/Tumor Suppressor Protein p53

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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