TP53 gene mutations and cytogenetic aberrations in tumor cells of patients with primary mediastinal B-cell large cell lymphoma

Introduction. TP53 gene mutations and cytogenetic abnormalities ( MYC /8q24, BCL2 /18q21, BCL6 /3q27, del17p13, and complex karyotype) play an important role in prognosis and therapy selection for various lymphoproliferative diseases. However, their signifi cance in the pathogenesis and prognosis of primary mediastinal B-cell large cell lymphoma (PMBCL) remains poorly understood and warrants further investigation. Aim: to assess the frequency of TP53 gene mutations and cytogenetic aberrations ( MYC /8q24, BCL2 /18q21, BCL6 /3q27, del17p13, and complex karyotype) and their impact on treatment outcomes in PMBCL. Materials and methods. The study included 51 patients who underwent therapy using the response-adapted DA-EPOCHR protocol from 2012 to 2024. Analysis of TP53 mutations (exons 4–10) was performed using high-throughput sequencing (n = 31/51 (61 %)). FISH analysis was conducted to identify chromosomal abnormalities involving the loci of MYC /8q24, BCL2/ 18q21, BCL6 /3q27, and del17p13 ( n = 31/51 (61 %)), and standard karyotyping was carried out ( n = 31/51 (61 %)). Due to the low mitotic activity of tumor cells, suffi cient mitoses were obtained in only 16/31 (52%) PMBCL samples. Results. TP53 mutations were identifi ed in 4/31 (13%) patients, with three of these mutations classifi ed as pathogenic. Isolated translocations involving MYC /8q24 and BCL6 /3q27 loci were detected in 2/31 (6 %) patients. Structural rearrangements of chromosome 17 in the TP53 locus and translocations involving the BCL2 /18q21 locus were not identifi ed in any case. At 36 months, overall survival in the TP53 -WT and TP53 -MUT groups was 85 % and 100 %, respectively ( p = 0.61). The relapse/progression rate was 33 % in TP53 -MUT patients and 20 % in TP53 -WT patients ( p = 0.35). Conclusion. The fi ndings demonstrate the rarity and lack of prognostic signifi cance of the investigated markers in PMBCL patients. These results underscore the need for further research to identify driver events in biologically discrete subtypes of aggressive B-cell lymphomas, as well as risk factors specifi c to each subtype. Such research will provide a foundation for the development of precision therapy approaches.