Document Detail

Significance of p53 mutations in patients with chronic lymphocytic leukemia: a sequential study of 30 patients.
MedLine Citation:
PMID:  11180073     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: In patients with B-cell chronic lymphocytic leukemia (CLL), considerable disease heterogeneity within clinical stages necessitates the search for relevant prognostic indicators, particularly those that may help to determine the need for early therapeutic intervention. In the current study, the authors investigated the role of p53 mutations and chromosomal abnormalities in 30 patients with CLL. METHODS: Thirty patients were screened for p53 mutations. Half of the group had aggressive disease characterized by leucocytosis, lymph node enlargement, organomegaly, and shortened tumor doubling time. Because 95% of p53 mutations reside in "hot-spot" regions of exons 5-9 of the p53 gene, the authors sequenced these exons completely for mutation detection. RESULTS: Sequence analysis identified p53 mutations in 14 of 30 patients that were distributed equally among patients with aggressive disease and nonaggressive disease. There were six mutations in exon 7, five mutations in exon 5, and one mutation each in exons 6 and 8. Five of 15 patients with clinically aggressive disease had mutations in exon 7. Only one patient with nonaggressive disease had an exon 7 mutation. Abnormal cytogenetics were present in 22 of 30 patients (73%). Most patients with the p53 mutation (13 of 14 patients; 93%) displayed abnormal cytogenetics. Twelve of 15 patients with aggressive disease and 9 of 15 patients with average disease exhibited abnormal karyotypes. CONCLUSIONS: The presence of p53 mutations did not predict clinical behavior or disease outcome, although the frequency of mutations appears to be higher than reported previously. In this study, mutations of exon 7 (5 of 6 patients) occurred in patients with clinically aggressive disease. The significance of this observation warrants further examination.
N Barnabas; M Shurafa; D L Van Dyke; S R Wolman; D Clark; M J Worsham
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer     Volume:  91     ISSN:  0008-543X     ISO Abbreviation:  Cancer     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-03-01     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  285-93     Citation Subset:  AIM; IM    
Department of Pathology, Henry Ford Health System, Detroit, Michigan 48202, USA.
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MeSH Terms
Exons / genetics
Genes, p53 / genetics*
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy,  genetics*,  pathology
Mutation / genetics*
Polymorphism, Single-Stranded Conformational
Sequence Analysis, DNA
Grant Support

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