p53 mutation/deletion profile in a small cohort of the Omani population with diffuse large B-cell lymphoma

ABSTRACT

Mutations/deletions affecting the TP53 gene are considered an independent marker predicting a poor prognosis for patients with diffuse large B-cell lymphoma [DLBCL]. A cohort within a genetically isolated population was investigated for p53 mutation/deletion status. Deoxyribonucleic acid [DNA] samples were extracted from 23 paraffin-embedded blocks obtained from DLBCL patients, and subjected to polymerase chain reaction [PCR] amplification and sequencing of exons 4-9 of the p53 gene. While 35% of patients analysed displayed allelic deletions [P <0.01], immunohistochemical analysis revealed a mutation rate of 69.5%. It is noteworthy that the rate of p53 mutations/deletions in this small cohort was found to be higher than that previously reported in the literature. Interestingly, patients with p53 mutations displayed a better overall survival when compared to those without. The survival of patients treated with rituximab-containing combination chemotherapy was significantly better than those who did not receive rituximab [P <0.05]. Furthermore, a modelling analysis of the deleted form of p53 revealed a huge structural change affecting the DNA-binding domain. The TP53 mutation/deletion status plays a role in mechanism[s] ruling the pathogenesis of DLBCL and may be useful for stratifying patients into distinct prognostic subsets