title: IL-10 -1082 SNP and IL-10 in primary CNS and vitreoretinal lymphomas.
abstract: OBJECTIVE
  Most primary central nervous system lymphomas (PCNSLs) and primary vitreoretinal lymphomas (PVRLs) are B-cell lymphomas that produce high levels of interleukin (IL)-10, which is linked to rapid disease progression. The IL-10                   (-1082) G → A polymorphism (IL-10 SNP) is associated with improved survival in certain non-CNS lymphoma patients. PDCD4 is a tumor suppressor gene and upstream regulator of IL-10. This study examined the correlation between the IL-10 SNP, PDCD4 mRNA expression, and IL-10 expression (at transcript and protein levels) in these lymphoma cells.
  
  
  METHODS
  Single-nucleotide polymorphism (SNP)-typing at IL-10                   (-1082) was performed after microdissecting cytospun PVRL cells from 26 specimens. Vitreal IL-10 and IL-6 levels were measured by ELISA. PCNSL cells from 52 paraffin-embedded sections were microdissected and SNP typed on genomic DNA. RT-PCR was performed to analyze expression of IL-10 and PDCD4 mRNA. IL-10                   (-1082) SNP typing was performed on blood samples of 96 healthy controls. We measured IL-10                   (-1082) SNP expression in 26 PVRLs and 52 PCNSLs and examined its relationship with IL-10 protein and gene expression, respectively.
  
  
  RESULTS
  More PVRL patients expressed one copy of the IL-10                   (                     -1082                   )                             G → A SNP with the GA genotype compared to controls. The frequencies of the three genotypes (AA, AG, GG) significantly differed in PVRL versus controls and in PCNSL versus controls. In PVRLs, the vitreal IL-10/IL-6 ratio was higher in IL-10                   (-1082) AG and IL-10                   (-1082) AA patients, compared to IL-10                   (-1082) GG patients. IL-10 mRNA expression was higher in IL-10                   (-1082) AG and IL-10                   (-1082) AA PCNSLs, compared to IL-10                   (-1082) GG PCNSLs. No correlation was found between IL-10 and PDCD4 expression levels in 37 PCNSL samples.
  
  
  CONCLUSIONS
  PVRL and PCNSL patients had similar IL-10                   (-1082) A allele frequencies, but genotype distributions differed from healthy controls. The findings suggest that the IL-10                   (-1082) A allele is a risk factor for higher IL-10 levels in PVRLs and PCNSLs. Higher IL-10 levels have been correlated with more aggressive disease in both PVRLs and PCNSLs, making this finding an important and potentially clinically significant observation.
authors.affiliation: Immunopathology Section, Laboratory of Immunology National Institutes of Health, 10 Center Drive, 10/10 N103, NIH/NEI, Bethesda, MD, 20892-1857, USA.
authors.forename: Hema L
authors.initials: HL
authors.lastname: Ramkumar
authors.forename: De Fen
authors.initials: DF
authors.lastname: Shen
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Tuo
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Coupland
authors.forename: Justine R
authors.initials: JR
authors.lastname: Smith
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005134:Eye Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D019572:Retinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014822:Vitreous Body / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D016753:Interleukin-10