American Association for Cancer Research
10780432ccr142116-sup-136368_1_supp_2763628_nfrjcx.docx (84.18 MB)

Supplementary Figures S1-S3 from Genome-Wide Analysis Uncovers Novel Recurrent Alterations in Primary Central Nervous System Lymphomas

Download (84.18 MB)
journal contribution
posted on 2023-03-31, 18:20 authored by Esteban Braggio, Scott Van Wier, Juhi Ojha, Ellen McPhail, Yan W. Asmann, Jan Egan, Jackline Ayres da Silva, David Schiff, M. Beatriz Lopes, Paul A. Decker, Riccardo Valdez, Raoul Tibes, Bruce Eckloff, Thomas E. Witzig, A. Keith Stewart, Rafael Fonseca, Brian Patrick O'Neill

Supplementary Figures S1-S3. Supplementary Figure S1. Overview of copy number abnormalities identified in the cohort of PCNSL analyzed. Supplementary Figure S2. FISH screening of BCL6 break apart (A, left box), IGH-BCL6 fusion (A, right box), PRKCD (B) and TOX (C). Supplementary Figure S3. Univariate overall survival analysis based on the status of 6q21 (PRDM1).



Purpose: Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma confined to the central nervous system. Whether there is a PCNSL-specific genomic signature and, if so, how it differs from systemic diffuse large B-cell lymphoma (DLBCL) is uncertain.Experimental Design: We performed a comprehensive genomic study of tumor samples from 19 immunocompetent PCNSL patients. Testing comprised array-comparative genomic hybridization and whole exome sequencing.Results: Biallelic inactivation of TOX and PRKCD was recurrently found in PCNSL but not in systemic DLBCL, suggesting a specific role in PCNSL pathogenesis. In addition, we found a high prevalence of MYD88 mutations (79%) and CDKN2A biallelic loss (60%). Several genes recurrently affected in PCNSL were common with systemic DLBCL, including loss of TNFAIP3, PRDM1, GNA13, TMEM30A, TBL1XR1, B2M, CD58, activating mutations of CD79B, CARD11, and translocations IgH-BCL6. Overall, B-cell receptor/Toll-like receptor/NF-κB pathways were altered in >90% of PNCSL, highlighting its value for targeted therapeutic approaches. Furthermore, integrated analysis showed enrichment of pathways associated with immune response, proliferation, apoptosis, and lymphocyte differentiation.Conclusions: In summary, genome-wide analysis uncovered novel recurrent alterations, including TOX and PRKCD, helping to differentiate PCNSL from systemic DLBCL and related lymphomas. Clin Cancer Res; 21(17); 3986–94. ©2015 AACR.

Usage metrics

    Clinical Cancer Research



    Ref. manager