Heterogeneous p53 mutations in a Burkitt lymphoma from an AIDS patient with monoclonal c-myc and VDJ rearrangements

Paola Campomenosi, Gilberto Fronza, Laura Ottaggio, Silvio Roncella, Alberto Inga, Massimo Bogliolo, Paola Monti, Paola Assereto, Francesca Moro, Giovanna Cutrona, Simonetta Bozzo, Nicholas Chiorazzi, Angelo Abbondandolo, Manlio Ferrarini

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Abstract

This study investigates the timing of p53 mutations detected in the malignant cells of a Burkitt's lymphoma cell line (BRG-P) with respect to other maturation or transforming events. The BRG-P cell line, derived from an AIDS patient, was of special value since it displayed subclones that had undergone an isotype switch from IgM to IgA1 (BRG-M and BRG-A cells). BRG-M and BRG-A cells were characterized by the same monoclonal c-myc and VDJ rearrangements and by the expression of Ig receptors with specificity for a 45 kDa protein of human breast cells. Analysis of p53 mutations in the different BRG subclones showed that 1) BRG-M cells displayed 2 different p53 mutations in trans; since the original BL cells also showed the same mutations, this finding indicated that both occurred in vivo; 2) one of the p53 alleles of BRG-A cells was lost, while the other showed a mutation different from those seen in BRG-M cells; and 3) all 3 mutations observed in BRG-M or BRG-A cells resulted in the functional inactivation of the transcriptional activation function of p53. Together, our data demonstrate that p53 mutations were relatively late events during lymphomagenesis. Moreover, in view of the role of p53 in cell apoptosis, it is conceivable that BRG cells were subjected to a strong selective pressure that favored p53 inactivation. Such inactivation was possibly required to counterbalance other potentially apoptotic events, including the presence of a deregulated c-myc oncogene and signals delivered by the host environment in situ.

Original languageEnglish
Pages (from-to)816-821
Number of pages6
JournalInternational Journal of Cancer
Volume73
Issue number6
Publication statusPublished - Dec 10 1997

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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