Distribución e impacto pronóstico de subtipos de LymphGen en linfoma difuso de células B grandes coreano utilizando...

Several molecular subclassifications of diffuse large B-cell lymphoma (DLBCL) with prognostic and therapeutic potential have been proposed; however, their 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 targeted NGS panel for clinical use comprising 121 lymphoma-related genes. We further assessed quality control (QC) metrics, copy-number reliability, and benchmarking performance against an external reference dataset (MSKCC-IMPACT). The LymphGen subtype distribution varied across different entities of DLBCL. DLBCL-not otherwise specified (DLBCL-NOS) samples (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%). 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 to 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 MYC/BCL2 double-expression (DE) DLBCL. Kaplan-Meier analysis of R-CHOP-treated patients with DLBCL-NOS revealed that those 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.