GRCh38 · COSMIC v100

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Reference

Genome-wide analysis uncovers novel recurrent alterations in primary central nervous system lymphomas.

Paper ID

COSP39826

Authors

Braggio E, Van Wier S, Ojha J, McPhail ER, Assmann Y, Egan JB, Ayres-Silva J, Schiff D, Lopes B, Decker PA, Valdez R, Tibes R, Eckloff BW, Witzig TE, Stewart AK, Fonseca R and O'Neill BP

Affiliation

Hematologic Oncology, Mayo Clinic [email protected].

Journal

Clinical cancer research : an official journal of the American Association for Cancer Research, 2015
ISSN: 1078-0432
PMID: 25991819 (view at PubMed or Europe PMC)

Abstract

Purpose: Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma confined to the CNS. Whether there is a PCNSL-specific genomic signature and, if so, how it differs from systemic diffuse large B-cell lymphoma (DLBCL) is uncertain.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 were recurrently found in PCNSL but not in systemic DLBCL, suggesting a specific role in PCNSL pathogenesis. Additionally, 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, BCR/TLR/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.

Paper Status

Curated