title: Genome-Wide Analysis Uncovers Novel Recurrent Alterations in Primary Central Nervous System Lymphomas.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Mayo Clinic, Scottsdale, Arizona. braggio.esteban@mayo.edu.
authors.forename: Esteban
authors.initials: E
authors.lastname: Braggio
authors.affiliation: Mayo Clinic, Scottsdale, Arizona.
authors.forename: Scott
authors.initials: S
authors.lastname: Van Wier
authors.affiliation: Mayo Clinic, Scottsdale, Arizona.
authors.forename: Juhi
authors.initials: J
authors.lastname: Ojha
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Ellen
authors.initials: E
authors.lastname: McPhail
authors.affiliation: Mayo Clinic, Jacksonville, Florida.
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.affiliation: Mayo Clinic, Scottsdale, Arizona.
authors.forename: Jan
authors.initials: J
authors.lastname: Egan
authors.affiliation: National Institute of Cancer, Brazil.
authors.forename: Jackline Ayres
authors.initials: JA
authors.lastname: da Silva
authors.affiliation: University of Virginia, Charlottesville, Virginia.
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.affiliation: University of Virginia, Charlottesville, Virginia.
authors.forename: M Beatriz
authors.initials: MB
authors.lastname: Lopes
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.affiliation: Mayo Clinic, Scottsdale, Arizona.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Valdez
authors.affiliation: Mayo Clinic, Scottsdale, Arizona.
authors.forename: Raoul
authors.initials: R
authors.lastname: Tibes
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Bruce
authors.initials: B
authors.lastname: Eckloff
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.affiliation: Mayo Clinic, Scottsdale, Arizona.
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
authors.affiliation: Mayo Clinic, Scottsdale, Arizona.
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Brian Patrick
authors.initials: BP
authors.lastname: O'Neill
mesh_terms: D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002869:Chromosome Aberrations; D002896:Chromosomes, Human, Pair 6; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D059472:Exome; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D059785:Karyotype; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D009154:Mutation; D011379:Prognosis