IBCL-365 Variety of Mutations In Russian B-Cell Lymphoma Patients

Abstract

TP53 plays a key role in almost all cellular processes. Mutations in this gene are found in most types of neoplasms. Among hematological malignancies, TP53 lesions are the most actively studied in CLL, although available data for other lymphomas remains limited. To study the frequency and diversity of TP53 mutations in Russian patients with B-cell lymphomas. The study included 145 DNA samples from patients with B-cell lymphomas: 53 patients with DLBCL, 47 patients with MCL, and 45 patients with FL, 16 of whom experienced transformation to DLBCL. Mutations in TP53 (exons 4-10) in most samples were detected using NGS (138 patients) or Sanger sequencing (7 patients). The clinical significance of detected variants was assessed using the Seshat online tool based on the UMD TP53 database. TP53 mutations were detected in 24 DLBCL patients (45.4%), 21 of which were missense mutations, 2 were splicing site mutations, and 1 was an insertion. Sixteen variants were identified as (probably) pathogenic, and 8 mutations were of unclear significance. Del17p was simultaneously detected in 7 patients with TP53 mutations (of 11 examined). In MCL patients, mutations were found in 19 cases (40%). Eighteen were missense mutations, and 1 was a splicing mutation. Sixteen variants were identified as (probably) pathogenic, and 3 were variants of unclear significance. Chromosome 17 abnormalities were found in 7 MCL patients with TP53 mutations of 11 studied. In FL patients, TP53 mutations were detected in 12 cases (26.7%). Eight were missense mutations, 2 were nonsense mutations, 1 was a splicing mutation, and 1 was a deletion. Nine variants were recognized as (probably) pathogenic, and 2 were variants of unclear significance. Only 1 patient of 6 examined had del17p. The frequency of TP53 mutations in our cohort of patients with B-cell lymphomas was significantly higher than the frequency reported for other cohorts. This bias may be due to differences in patient selection. We are planning further studies examining the type of mutations, allelic loads, and combinations with other chromosome 17 lesions in association with the disease course.