PB2066 DAMAGE OF THE TP53 GENE POLYADENYLATION SIGNAL IN DLBCL

Abstract

Background:Single nucleotide replacement rs78378222 lead to change of the normal TP53 gene polyadenylation signal and cause disorders of processing of 3′‐end of mRNA. The experimental data have suggested that rare allele C of the rs78378222 leads to much lower level of TP53 expression and decrease the apoptosis induction level in cells under the influence of genotoxic agents in comparison with allele A. Thus, rs78378222 is thought to be the unique allele variant of TP53 gene with the reduced p53 function.Aims:The purpose of the present study was to reveal the frequency of the rs78378222 of TP53 in tumor tissue of the patients with diffuse large B‐cell lymphoma (DLBCL).MethodsGenomic DNA was isolated from formalin‐embedded paraffin blocks of lymph nodes and extranodal tumor lesions biopsies of 92 patients with DLBCL by phenol‐chloroform extraction method using guanidine. The tissue sections containing at least 70‐80% of the tumor cells were taken. Genotyping of the rs78378222 was performed by the PCR‐RFLP method. To confirm the presence of rare allele C of the rs78378222 Sanger's direct sequencing was performed.Results:The frequency of the rs78378222 in DLBCL tumor tissue was 9/92 (9.8%). It was noted that 5 of 9 patients had minor allele C in the homozygous state. Since the detection of cases of the rare homozygous genotype C/C of the rs78378222 in normal tissue has not described previously, the received results indicated a loss of heterozygosity in the TP53 gene in DLBCL tumor tissue of rs78378222 carriers. Only two of these cases were combined with mutations in the gene. In three cases ‐ loss of heterozygosity was the only aberration in TP53.Summary/Conclusion:Aberrations in 3′‐UTR of TP53 gene may be a universal carcinogenesis mechanism, playing role in pathogenesis of DLBCL as well. The loss of normal allele A rs78378222 stimulates the significant growth of cells malignant potential.