Fig 1.
Genetic Classification by Lymphgen. A.
Genetic classification by Lymphgen identified a specific subgroup in fifty-three cases (49%), while the remaining fifty-five cases were classified as unclassified (molecular subtype NOS/Other). B. DLBCL cases exhibited a similar distribution of genetic subtypes, with ST2 being the most prevalent subtype. C. A Sankey plot illustrating the genetic subtyping by Lymphgen across various large B-cell lymphoma entities. Notably, some entities, such as HGBCL/DLBCL DH, display homogeneous genetic features (i.e., EZB subtype). D. A Sankey plot depicting the genetic subtyping by Lymphgen according to cell of origin subtypes in DLBCL NOS cases. As shown, EZB is preferentially associated with GCB-type DLBCL, while both MCD and BN2 subtypes demonstrate a higher prevalence in non-GCB-type DLBCL tumors.
Fig 2.
Analysis of MYC target pathways in DLBCL cases based on genetic subtype.
MYC gene targets exhibited significant mutations in cases with specific genetic subtypes, in contrast to molecular NOS cases (Chi-square p < 0.001). Notably, there were no MYC target mutations observed in cases classified as pure MCD genetic subtype. B. Analysis of the TP53 pathway in DLBCL cases according to genetic subtype. TP53 heterozygous deletions were identified through predicted copy number alterations (CNAs) in seven out of 86 DLBCL cases (1 A53, 2 ST2, and 4 molecular NOS/Other). Somatic mutations in the TP53 pathway (including mutations in ATM, TP53, RPS6KA3, MDM4, CHECK2, and MDM2) were detected in 23 out of 46 (50%) genetically classified cases and in 9 out of 40 (22%) cases from the molecular NOS group. Somatic mutations in the TP53 pathway were significantly enriched in cases with defined genetic subtypes (Chi-square, p < 0.001). Reason: Improved clarity, readability, and technical accuracy while maintaining the original meaning.
Fig 3.
A. Prevalence of the ST2 genetic subtype in cases of plasmablastic lymphoma. B. Detailed analysis of LymphGen genetic features, highlighting an enrichment of genes associated with the ST2 subtype. C. Overview of protein localization for recurrent somatic mutations in TET2, TRRAP, PRRC2C, PABPC1, and STAT3.
Fig 4.
A. Enrichment of the RTK-RAS pathway in plasmablastic lymphoma. Note the recurrent mutations in the MAPK/ERK pathway, including NF1, BRAF, NRAS, KRAS, MAPK3, as well as NTRK2, NTRK3, and ROS1. B1. Analysis of TP53 target pathways in plasmablastic lymphoma cases according to genetic subtype. Structural aberrations of TP53 (heterozygous/homozygous loss) were absent in the twenty-two plasmablastic lymphoma cases. The TP53 pathway was significantly mutated in cases with ST2 genetics. B2. Analysis of MYC target pathways in plasmablastic lymphoma cases based on genetic subtype. MYC targets were recurrently mutated in this entity, particularly in cases with the ST2 and ST2/EZB genetic subtypes (4 out of 6 cases, 66%), regardless of the presence of MYC translocation as determined by FISH.