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

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