Primary central nervous system lymphoma (PCNSL) is an aggressive brain cancer characterized by a perivascular accumulation of malignant cells with lymphoid characteristics. Without translatable knowledge of the mechanisms of PCNSL development and progression treatment falls on conventional managements such as radiotherapy and chemotherapy. However, these treatments are intense, and the quality of survival is often poor.
Unlike systematic diffuse large B-cell lymphomas (DLBCL), only a limited number of genetic studies have been performed to better understand the genomic landscape of PCNSL due to the lack of available tissue specimens.
Mayo Clinic researchers, first author Esteban Braggio, Ph.D., conducted a study published in Clinical Cancer Research to determine whether there is a PCNSL-specific genomic signature and, if so, how it differs from DLBCL.
In the study, researchers performed a comprehensive genomic study of tumor samples from 19 immunocompetent PCNSL patients. Testing comprised of array-comparative genomic hybridization and whole exome sequencing.
Based on the results, Mayo Clinic researchers identified a related genomic landscape between PCNSL and DLBCL and confirmed the existence of a specific molecular signature in PCNSL characterized by recurrent alterations in PRKCD and TOX. Furthermore, this comprehensive genomic study identified targetable pathways in the disease. PCNSL is an aggressive malignancy and better and more specific treatments are needed. The identification of mutations affecting the BCR, TLR, and NF-κB signaling pathways in most of the PCNSL cases highlights the potential value of these pathways to be targeted in PCNSL.