IL-10 -1082 SNP and IL-10 in primary CNS and vitreoretinal lymphomas.

Abstract

OBJECTIVES:

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.

MATERIALS AND 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: Hema L Ramkumar, De Fen Shen, Jingsheng Tuo, Rita M Braziel, Sarah E Coupland, Justine R Smith, Chi-Chao Chan
• Journal: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie (Graefes Arch Clin Exp Ophthalmol) Vol. 250 Issue 10 Pg. 1541-8 (Oct 2012) ISSN: 1435-702X [Electronic] Germany
• PMID: 22628023 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• PDCD4 protein, human
• RNA, Messenger
• RNA-Binding Proteins
• Interleukin-10

Topics

• Adult
• Aged
• Aged, 80 and over
• Apoptosis Regulatory Proteins (genetics)
• Brain Neoplasms (genetics, metabolism, pathology)
• Enzyme-Linked Immunosorbent Assay
• Eye Neoplasms (genetics, metabolism, pathology)
• Female
• Gene Frequency
• Genotype
• Humans
• Interleukin-10 (genetics)
• Lymphoma, B-Cell (genetics, metabolism, pathology)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• RNA, Messenger (metabolism)
• RNA-Binding Proteins (genetics)
• Retinal Neoplasms (genetics, metabolism, pathology)
• Reverse Transcriptase Polymerase Chain Reaction
• Vitreous Body (metabolism, pathology)
• Young Adult