Molecular genetic characteristics and pathogenetic mechanisms of mantle cell lymphoma: a cohort study

BACKGROUND: In addition to the characteristic t(11;14) translocation, the genome of mantle cell lymphoma is distinguished by numerous secondary chromosomal aberrations and molecular genetic alterations. AIM: This study aimed to assess the mutational profile of mantle cell lymphoma, identify the most frequent genetic aberrations, and determine their impact on overall survival. METHODS: Twenty-four patients with classical stage III–IV mantle cell lymphoma were included. All patients underwent conventional cytogenetic analysis, fluorescence in situ hybridization, and next-generation sequencing. Karyotypes were interpreted in accordance with the International System for Human Cytogenomic Nomenclature (ISCN). Moreover, survival functions were estimated using the Kaplan–Meier method with the log-rank test. The relationship between survival time and independent variables was evaluated using univariate and multivariate Cox regression analyses. RESULTS: Conventional cytogenetic analysis determined a normal karyotype in 19 (79.2%) patients. The t(11;14) translocation was detected in three patients, 17p deletion in two (8%), and a complex karyotype in two (8%). Fluorescence in situ hybridization analysis identified t(11;14) translocation in 16 (67%) patients, TP53/17p13 deletion in 4 (17%), and MYC/8q24 rearrangement in 3 (12.5%). TP53/17p13 deletion induced an independent negative effect on overall survival (p = 0.020). NGS revealed the most frequent mutations in ATM (36%), RYR1 (27%), BCR (27%), and KMT2D (23%) genes. Significant associations were observed between FAT1 and BCR (p = 0.013), MGA and KMT2D (p = 0.024), and DNMT3A and KMT2D (p = 0.043) mutations. Among the detected variants, the ATM mutation predicted poor overall survival; however, its statistical significance was lost after adjusting for TP53/17p13 deletion (p = 0.099). CONCLUSION: Analysis of the mutational profile revealed the most frequent aberrations—mutations in ATM, BCR, and KMT2D genes—in mantle cell lymphoma, which potentially contribute to the tumor’s pathogenesis.