From marginal zone lymphoma to aggressive diffuse large B-cell lymphoma: a whole-exome and clinicopathological characteristics analysis of transformed lymphoma

Abstract Background Transformed lymphoma occurs when indolent lymphoma transforms into more aggressive lymphoma usually associated with poor prognosis. Methods In this study, we analyzed the immunophenotypes, prognostic factors, and outcomes of 35 patients with transformed lymphoma from among 306 marginal zone lymphoma (MZL), 544 follicular lymphoma (FL), and 871 chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) cases. In addition, we performed whole-exome sequencing study of 7 transformed MZL (tMZL) cases. Results Our results demonstrate that the median time from indolent lymphoma diagnosis to transformed DLBCL was 35 months (range, 14–53 months). The 5-year overall survival (OS) and progression-free survival (PFS) rates after histological transformation (HT) were 50% and 26%, respectively. Kaplan-Meier survival analysis revealed that asynchronous HT and transformed CLL/SLL (tCLL/SLL) were significant adverse prognostic factors for OS after DLBCL HT. Our study found that TNFAIP3 was the most frequently mutated gene in tMZL samples. We identified mutations involvement in chromatin remodeling ( CREBBP and EP300 ) and regulators of NF-κB signaling( TNFAIP3, BCL10, MYD88, CD79B, and CARD11 ) were affected in tMZL. Conclusion Whole-exome sequencing and copy-number analysis revealed that tMZL derives from the divergent evolution of an ancestral common progenitor clone (CPC). Collectively, this study provides clinicopathological characteristics of three common types of transformed lymphomas and the genetic profile of tMZL with diagnostic and therapeutic implications.