Significance of p53 mutations in patients with chronic lymphocytic leukemia: A sequential study of 30 patients

Nandita Barnabas, Muhammad Shurafa, Daniel L. Van Dyke, Sandra R. Wolman, Damon Clark, Maria J. Worsham

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)285-293
Number of pages9
JournalCancer
Volume91
Issue number2
DOIs
StatePublished - Jan 15 2001

Keywords

  • Aggressive disease
  • B-cell chronic lymphocytic leukemia
  • Cytogenetics
  • Leucocytosis
  • Lymph nodes
  • Organomegaly
  • Sequencing
  • Single-strand conformation polymorphism
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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