title: Del(6)(q22) and BCL6 rearrangements in primary CNS lymphoma are indicators of an aggressive clinical course.
abstract: OBJECTIVE
  Primary CNS lymphoma (PCNSL) is an aggressive lymphoma but clinically validated biologic markers that can predict natural history to tailor treatment according to risk are lacking. Several genetic changes including BCL6 rearrangements and deletion of 6q22, containing the putative tumor suppressor gene PTPRK, are potential risk predictors. Herein we determined the prevalence and survival impact of del(6)(q22) and BCL6, immunoglobulin heavy chain (IGH), and MYC gene rearrangements in a large PCNSL cohort treated in a single center.
  
  
  METHODS
  Interphase fluorescence in situ hybridization was performed using two-color probes for BCL6, MYC, IGH-BCL6, and del(6)(q22) on thin sections of 75 paraffin-embedded samples from 75 HIV-negative, immunocompetent patients newly diagnosed with PCNSL. Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and proportional hazards regression adjusting for age, deep structure involvement, and high-dose methotrexate (HDMTX) treatment.
  
  
  RESULTS
  The prevalence of del(6)(q22) and BCL6, IGH, and MYC translocations was 45%,17%, 13%, and 3%, respectively. The presence of del(6)(q22) and/or a BCL6 translocation was associated with inferior overall survival (OS; P = .0097). The presence of either del(6)(q22) alone or a BCL6 translocation alone was also associated with inferior OS (P = .0087). Univariable results held after adjusting for age, deep structure involvement, and HDMTX.
  
  
  CONCLUSIONS
  Del (6)(q22) and BCL6 rearrangements are common in PCNSL and predict for decreased OS independent of deep structure involvement and HDMTX. Unlike systemic diffuse large B-cell lymphoma, del(6)(q22) is common and IGH translocations are infrequent and usually involve BCL6 rather than BCL2, suggesting a distinct pathogenesis.
authors.affiliation: Department of Pathology, CellNetix Pathology, Olympia, WA, USA.
authors.forename: Francois M
authors.initials: FM
authors.lastname: Cady
authors.forename: Brian Patrick
authors.initials: BP
authors.lastname: O'Neill
authors.forename: Mark E
authors.initials: ME
authors.lastname: Law
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.forename: David M
authors.initials: DM
authors.lastname: Kurtz
authors.forename: Caterina
authors.initials: C
authors.lastname: Giannini
authors.forename: Alyx B
authors.initials: AB
authors.lastname: Porter
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kurtin
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Johnston
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.forename: Ellen D
authors.initials: ED
authors.lastname: Remstein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D051560:Proto-Oncogene Proteins c-bcl-6; D017384:Sequence Deletion
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6