An improved algorithm for genetic diagnostics of aggressive B-cell lymphomas in pediatric oncohematology: the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Objective. To improve the stratification algorithm for aggressive B-cell lymphomas in children based on the analysis of genetic changes in the genes TP53, MYC, BCL2, BCL6 and the long arm of chromosome 11 (11q). Material and methods. A comprehensive cytogenetic and molecular genetic analysis of tumor samples was carried out using NGS and FISH methods. Rearrangements of the MYC locus and the presence of translocations with different chromosomal partners were investigated, as well as the analysis of mutations and deletions of the TP53 gene. The presence of MYC, BCL2, BCL6 rearrangements and 11q aberrations was investigated as part of the algorithm. Results. It has been shown that the classical translocation, t(8;14)(q24;q32) MYC::IGH, is detected in 77% of cases with typical Burkitt lymphoma histology. This translocation was not present in 23% of the samples. In a group of cases with classic histology of Burkitt lymphoma, where the t(8;14)(q24;q32) translocation was absent, rare genetic variations were identified — 11q gain/loss, and atypical FISH patterns indicative of complex genetic changes. TP53 mutations were detected in 26-30% of cases, localized mainly in the DNA-binding domain. A wide range of genetic changes has been identified, including monoallelic TP53 deletions and atypical FISH patterns that require attention and additional research. Conclusion. An improved diagnostic algorithm based on the combined use of FISH and NGS methods makes it possible to increase the accuracy of identification of genetic subtypes of aggressive B-cell lymphomas in children. This helps to categorize the diagnosis based on the molecular and genetic characteristics of the tumor, paving the way for improved prognosis and treatment effectiveness.