Genome-Wide Analysis Uncovers Novel Recurrent Alterations in Primary Central Nervous System Lymphomas

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. We performed a comprehensive...

Full description

Saved in:

Bibliographic Details
Published in:	Clinical cancer research Vol. 21; no. 17; pp. 3986 - 3994
Main Authors:	Braggio, Esteban, Van Wier, Scott, Ojha, Juhi, McPhail, Ellen, Asmann, Yan W, Egan, Jan, da Silva, Jackline Ayres, Schiff, David, Lopes, M Beatriz, Decker, Paul A, Valdez, Riccardo, Tibes, Raoul, Eckloff, Bruce, Witzig, Thomas E, Stewart, A Keith, Fonseca, Rafael, O'Neill, Brian Patrick
Format:	Journal Article
Language:	English
Published:	United States 01-09-2015
Subjects:	Central Nervous System Neoplasms - genetics Central Nervous System Neoplasms - metabolism Central Nervous System Neoplasms - mortality Chromosome Aberrations Chromosomes, Human, Pair 6 Comparative Genomic Hybridization DNA Copy Number Variations Exome Genetic Variation Genome-Wide Association Study High-Throughput Nucleotide Sequencing Humans Karyotype Lymphoma, Non-Hodgkin - genetics Lymphoma, Non-Hodgkin - metabolism Lymphoma, Non-Hodgkin - mortality Mutation Prognosis
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. We performed a comprehensive genomic study of tumor samples from 19 immunocompetent PCNSL patients. Testing comprised array-comparative genomic hybridization and whole exome sequencing. 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. In summary, genome-wide analysis uncovered novel recurrent alterations, including TOX and PRKCD, helping to differentiate PCNSL from systemic DLBCL and related lymphomas.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1078-0432 1557-3265
DOI:	10.1158/1078-0432.ccr-14-2116