ScholarWorks@성균관대학교

초록

Several molecular subclassifications of diffuse large B-cell lymphoma (DLBCL) with prognostic and therapeutic potential have been proposed; however, validation in diverse populations and real-world clinical settings remains limited. We investigated the genetic subtypes of Korean DLBCL using the LymphGen classifier and an institutionally developed 121-gene targeted next-generation sequencing (NGS) panel. We also assessed quality control metrics, copy number reliability, and benchmarking performance against an external reference data set (Memorial Sloan Kettering Cancer Center–Integrated Mutation Profiling Actionable Cancer Targets). LymphGen subtypes differed by entity. Patients with DLBCL, not otherwise specified (DLBCL-NOS; n = 123) were classified as MCD (25.2%), A53 (14.6%), ST2 (7.3%), BN2 (5.7%), EZB (3.3%), composite EZB/ST2 (1.6%), and unclassified (“other”; 42.3%). Patients with primary DLBCLs of the central nervous system (n = 77) were classified as MCD (70.1%), composite MCD/A53 (2.6%), A53 (3.9%), BN2 (2.6%), ST2 (1.3%), EZB (1.3%), and “other” (18.2%). Compared with Western cohorts, the LymphGen subtype distribution in our Korean DLBCL-NOS cohort differed notably, with MCD being significantly more prevalent. The MCD subtype tended to be associated with non–germinal center B-cell–like DLBCL and DLBCL with MYC/BCL2 double expression (DE). In R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin [vincristine], and prednisone)-treated DLBCL-NOS, patients with MCD, BN2, and A53 subtypes had poorer overall survival than those with EZB and ST2, particularly among patients with concurrent MYC/BCL2 DE. Using a clinically applicable NGS panel, we successfully implemented the LymphGen classification system. This study underscores the distinct genetic landscape of Korean DLBCL and highlights the utility of LymphGen in identifying high-risk subgroups, providing a basis for prognostic stratification and therapeutic optimization.

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