Molecular-genetic mechanisms and significance of p53 deregulation in diffuse large B-cell lymphoma

Researches aimed at studying the role of TP53 gene variability in the tumor progression of diff use large B-cell lymphoma(DLBCL) are among the most in-demand in both the fields of fundamental and applied oncohematology. However, until recently, the knowledge about the specific mechanisms of dysfunction of this gene and their clinical significance in DLBCL was largely limited.

This article is dedicated to the 300th anniversary of the Russian Academy of Sciences and describes the main scientific results of research of the molecular genetic mechanisms and the significance of p53 deregulation in DLBCL, conducted jointly by Novosibirsk State Medical University and the Research Institute of Therapy and Preventive Medicine – the Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences for many years.

A comprehensive study of TP53 variability due to functionally significant polymorphisms and haplotype structure, somatic mutations, promoter methylation, as well as allelic imbalance was carried out. A two-hit mechanism for dysfunction of this anti-oncogene in the formation of lymphoma has been established. The current underestimation of the frequency of aberrations in TP53 in DLBCL is shown due to ignoring synonymous mutations and changes in non-coding regions of the gene.

The deep involvement of TP53 in the processes of predisposition to development, initiation, progression and response of DLBCL to therapy has been proven.

The results obtained suggest that assessment of the function of the TP53 gene and understanding the specific mechanisms of its inactivation in each of the diagnosed cases of DLBCL may soon have direct access to personalized selection of therapy.

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