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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Cytology
Mantle-Cell Lymphoma
Cell Biology
Mutation
Genes
Polymerase chain reaction
Electrophoresis
Tumors
Exons
Proteins
Gels
Tissue
Antibodies
DNA
Denaturing Gradient Gel Electrophoresis
Survival
p53 Genes
Frozen Sections
Missense Mutation
Tumor Suppressor Genes

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.

p53 Mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. / Greiner, Timothy Charles; Moynihan, Michael J.; Chan, Wing C.; Lytle, Debra M.; Pedersen, Alex; Anderson, James R.; Weisenburger, Dennis D.

In: Blood, Vol. 87, No. 10, 15.05.1996, p. 4302-4310.

Research output: Contribution to journalArticle

Greiner, TC, Moynihan, MJ, Chan, WC, Lytle, DM, Pedersen, A, Anderson, JR & Weisenburger, DD 1996, 'p53 Mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis', Blood, vol. 87, no. 10, pp. 4302-4310.
Greiner TC, Moynihan MJ, Chan WC, Lytle DM, Pedersen A, Anderson JR et al. p53 Mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. Blood. 1996 May 15;87(10):4302-4310.
Greiner, Timothy Charles ; Moynihan, Michael J. ; Chan, Wing C. ; Lytle, Debra M. ; Pedersen, Alex ; Anderson, James R. ; Weisenburger, Dennis D. / p53 Mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. In: Blood. 1996 ; Vol. 87, No. 10. pp. 4302-4310.
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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.",
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AU - Chan, Wing C.

AU - Lytle, Debra M.

AU - Pedersen, Alex

AU - Anderson, James R.

AU - Weisenburger, Dennis D.

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N2 - 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.

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