p53 Mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis

Timothy Charles Greiner, Michael J. Moynihan, Wing C. Chan, Debra M. Lytle, Alex Pedersen, James R. Anderson, Dennis D. Weisenburger

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Abstract

Mutations of the p53 tumor suppressor gene have been described in several subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutations in mantle cell lymphoma (MCL) is unknown. We hypothesized that cases of MCL with a variant or high-grade cytology would have a higher likelihood of p53 mutations than typical MCL. We were also interested in the prognostic significance of p53 mutations in MCL. Therefore, a series of 53 well- characterized cases of MCL with DNA from 62 tissue samples was analyzed by the polymerase chain reaction with denaturing gradient gel electrophoresis for exons 5-8 of p53. Immunoperoxidase studies with the antibody DO-7 to p53 protein were also performed on frozen sections. We found mutations of the p53 gene in 8 of the 53 cases (15%) of MCL. Missense mutations predominated, and 50% of the mutations occurred at known p53 hotspot codons. Of 21 cases with variant cytology (ie, anaplastic or blastic), 6 (28.6%) had p53 mutations as compared with only 2 of 32 cases (6.3%) with typical MCL cytology (P = .05), and p53 mutations preceded the development of variant cytology in 2 patients. Overexpression of p53 protein was observed in 6 of the 8 cases (75%) with p53 mutations and in none of the 45 wild-type cases. The median survival of the cases with mutant p53 was only 1.3 years (all died), whereas the median survival of cases with germline p53 was 5.1 years (P = .023). These results suggest that mutations of p53 may be one mechanism involved in the development of variant forms of MCL and indicate that p53 mutations in MCL predict a poor prognosis.

Original languageEnglish (US)
Pages (from-to)4302-4310
Number of pages9
JournalBlood
Volume87
Issue number10
StatePublished - May 15 1996

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Greiner, T. C., Moynihan, M. J., Chan, W. C., Lytle, D. M., Pedersen, A., Anderson, J. R., & Weisenburger, D. D. (1996). p53 Mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. Blood, 87(10), 4302-4310.