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Primary Central Nervous System Lymphoma Tumor Biopsies Show Heterogeneity in Gene Expression Profiles, Genetic Subtypes, and in vitro Drug Sensitivity to Kinase Inhibitors
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Primary Central Nervous System Lymphoma Tumor Biopsies Show Heterogeneity in Gene Expression Profiles, Genetic Subtypes, and in vitro Drug Sensitivity to Kinase Inhibitors

Yuan Xiao Zhu, Jasper Ch Wong, Talal Hilal, Alanna Maguire, Jon Ocal, Katie Zellner, Xianfeng Chen, Brian K Link, Thomas M Habermann, Matthew J Maurer, …
medRxiv : the preprint server for health sciences
Cold Spring Harbor Laboratory
12/06/2024
DOI: 10.1101/2024.11.11.24316310
PMCID: PMC11643165
PMID: 39677423
url
https://doi.org/10.1101/2024.11.11.24316310View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Primary central nervous system lymphoma (PCNSL) is clinically challenging due to its location and small biopsy size, leading to a lack of comprehensive molecular and biologic description. We previously demonstrated that 91% of PCNSL belong to the activated B-cell-like (ABC) molecular subtype of diffuse large B-cell lymphoma (DLBCL). Here we investigated the expression of 739 cancer related genes in HIV (-) patients using NanoString digital gene expression profiling in 25 ABC-PCNSL and 43 ABC-systemic DLBCL, all tumors were EBV (-). We found that two-thirds of ABC-PCNSL samples had a transcriptional landscape distinct from ABC-systemic DLBCL samples. Of the 739 genes measured, 135 were identified as differentially expressed between these ABC-PCNSL and ABC-systemic DLBCL (p<0.05). Compared with ABC-systemic DLBCL, ABC-PCNSL showed higher gene expression in several cancer related gene sets including genes related to Hedgehog, DNA damage repair, Wnt and MAPK signaling. Hierarchical clustering 28 PCNSL samples (25 ABC and 3 GCB subtypes) identified two transcriptional subgroups, P1 (n=9) and P2 (n=19). P2 showed higher activities across most of the cancer related pathways and had a significantly shorter patient survival time (p<0.01). Whole exome sequencing showed that some distinct genetic features of PCNSL compared to DLBCL. The genetic subtypes ("LymphGen") of PCNSL consisted mainly of "MCD" and "Other" subtypes, which did not correlate with clinical survival. These data provide more information about unique characters of PCNSL, which may help to identify novel drug targets for developing therapeutic strategies.

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