P53 GENE MUTATION IN THE BONE-MARROW OF A PATIENT WITH DIFFUSE MIXED CELL-TYPE LYMPHOMA AT DIAGNOSIS PREDICTING EVENTUAL PROGRESSION TO LARGE-CELL LYMPHOMA

Mutations of the p53 tumor suppressor gene have been used as molecular genetic markers of disease and serve as a prognostic indicator in var ious malignancies including non-Hodgkin's lymphoma (NHL). Alterations in the p53 gene were investigated in a bone marrow sample from a NHL p atient admitted for autologous bone marrow transplantation. Diffuse mi xed small and large cell NHL, was initially diagnosed which eventually progressed to large cell lymphoma at relapse following poly-chemother apy. A sequential technique of polymerase chain reaction-mediated sing le-strand conformational polymorphism (PCR-SSCP) of the p53 gene revea led a shift in one band of exon 6 in the bone marrow, collected at the time of initial diagnosis. No mutations were detected in exons 5, 7, 8 and 9. Direct sequencing of exon 6 detected a single base change fro m G to C resulting in an amino acid substitution from glycine to histi dine. Results of this study and data reviewed from other publications suggest that the missense p53 mutation seen in this patient at the tim e of diagnosis may perhaps have been used to predict the eventual outc ome of the disease. This could, therefore, serve as an important genet ic disease marker particularly in bone marrow or peripheral blood samp les initially collected and cryopreserved for future possible autologo us transplantation.