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Blood DOI:10.1182/blood-2015-10-673236

Targetable genetic features of primary testicular and primary central nervous system lymphomas.

Publication TypeJournal Article
Year of Publication2016
AuthorsChapuy, B, Roemer, MGM, Stewart, C, Tan, Y, Abo, RP, Zhang, L, Dunford, AJ, Meredith, DM, Thorner, AR, Jordanova, ES, Liu, G, Feuerhake, F, Ducar, MD, Illerhaus, G, Gusenleitner, D, Linden, EA, Sun, HH, Homer, H, Aono, M, Pinkus, GS, Ligon, AH, Ligon, KL, Ferry, JA, Freeman, GJ, Van Hummelen, P, Golub, TR, Getz, G, Rodig, SJ, de Jong, D, Monti, S, Shipp, MA
JournalBlood
Volume127
Issue7
Pages869-81
Date Published2016 Feb 18
ISSN1528-0020
KeywordsCentral Nervous System Neoplasms, Female, Genetic Loci, Humans, Lymphoma, Large B-Cell, Diffuse, Male, Mediastinal Neoplasms, Neoplasm Proteins, Testicular Neoplasms, Translocation, Genetic
Abstract

Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal large B-cell lymphomas (LBCLs) with inferior responses to current empiric treatment regimens. To identify targetable genetic features of PCNSL and PTL, we characterized their recurrent somatic mutations, chromosomal rearrangements, copy number alterations (CNAs), and associated driver genes, and compared these comprehensive genetic signatures to those of diffuse LBCL and primary mediastinal large B-cell lymphoma (PMBL). These studies identify unique combinations of genetic alterations in discrete LBCL subtypes and subtype-selective bases for targeted therapy. PCNSLs and PTLs frequently exhibit genomic instability, and near-uniform, often biallelic, CDKN2A loss with rare TP53 mutations. PCNSLs and PTLs also use multiple genetic mechanisms to target key genes and pathways and exhibit near-uniform oncogenic Toll-like receptor signaling as a result of MYD88 mutation and/or NFKBIZ amplification, frequent concurrent B-cell receptor pathway activation, and deregulation of BCL6. Of great interest, PCNSLs and PTLs also have frequent 9p24.1/PD-L1/PD-L2 CNAs and additional translocations of these loci, structural bases of immune evasion that are shared with PMBL.

URLhttp://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=26702065
DOI10.1182/blood-2015-10-673236
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/26702065?dopt=Abstract

Alternate JournalBlood
PubMed ID26702065
PubMed Central IDPMC4760091
Grant ListP01 AI056299 / AI / NIAID NIH HHS / United States
R01 CA161026 / CA / NCI NIH HHS / United States