Classifying Germinal Center Derived Lymphomas—Navigate a Complex Transcriptional Landscape
Interdisciplinary Centre for Bioinformatics, University Leipzig (IZBI), 04107 Leipzig, Germany
Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, Germany
Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany
Institute of Human Genetics, Ulm University and Ulm University Medical Center, 89073 Ulm, Germany
Author to whom correspondence should be addressed.
Academic Editor: Blanca Scheijen
Received: 3 June 2022
Revised: 7 July 2022
Accepted: 11 July 2022
Published: 14 July 2022
Germinal center-derived B-cell lymphomas constitute a very heterogeneous group of neoplasms with diverse clinical presentations, prognoses, and responses to therapy. They divide into a series of subtypes, such as Diffuse Large B-cell lymphomas (DLBCL), Burkitt Lymphomas (BL), Follicular lymphomas (FL), and further, into several subclasses and rarer subtypes of finer granularity, which makes them one of the most heterogeneous cancer entities. Molecular classification schemes, first of all, derived from whole transcriptome gene expression data largely improved subtyping and functional understanding. Based on a whole transcriptome landscape of B-cell lymphoma, we show that one major caveat in the task of classification is represented by the rather fuzzy distribution of individual tumors without clear-cut borderlines between most of the subtypes, preventing their unambiguous association with clear-cut entities. This landscape is governed by the germinal center (GC) reaction and relates different subtypes to different states along the reaction path. We discuss the relatedness between the expression landscape and classifier signatures and their functional cell of origin background. This view helps to stratify lymphomas in terms of modular building blocks of signature genes and to interpret rarer subclasses in the context of larger ones.