High‐resolution genomic copy number profiling of primary intraocular lymphoma by single nucleotide polymorphism microarrays

Abstract

Primary intraocular lymphoma (PIOL) is a rare lymphoma. Because of difficulties in obtaining tissue samples, little is known about the disease's genetic features. In order to clarify these features, we carried out single nucleotide polymorphism array karyotyping of IOL using genomic DNA extracted from vitreous fluid. We analyzed 33 samples of IOLs consisting of 16 PIOLs, 12 IOLs with a central nervous system (CNS) lesion at diagnosis (IOCNSL), and five secondary IOLs following systemic lymphoma. All were B-cell type. We identified recurrent copy number (CN) gain regions in PIOLs, most frequently on chromosome 1q followed by 18q and 19q. Chromosome 6q was the most frequent loss region. Although these CN gain regions of PIOL were in common with those of IOCNSL, loss of 6q22.33 containing PTPRK and 9p21.3 containing CDKN2A were more frequently deleted in IOCNSL. Large CN loss in 6q was detected in three of four PIOL patients who had early CNS development and short survival periods, whereas long-term survivors did not have such deletions. There was a correlation between gain of the IL-10 gene located on 1q and intravitreal interleukin-10 concentration, which was higher in IOL than in benign uveitis. The results suggest that IOCNSL is a highly malignant form of PIOL that infiltrates into the CNS at an early stage. They also indicate that genetic differences between PIOL and primary CNS lymphoma need to be clarified.

High‐dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma

“…Along with those reports, our study confirmed that the detection of IL‐10 could reflect the status of the disease in the vitreous. We previously reported the correlation between gain of the IL‐10 gene and intravitreal IL‐10 concentration . These findings indicated that IL‐10 was secreted to the vitreous from the infiltrating lymphoma cells.…”

“…We previously reported the correlation between gain of the IL-10 gene and intravitreal IL-10 concentration. (2) These findings indicated that IL-10 was secreted to the vitreous from the infiltrating lymphoma cells.…”

“…It is a rare form of extranodal lymphoma, accounting for less than 1% of all non‐Hodgkin's lymphomas . Its morphological and genetic findings show that most cases are diffuse large B‐cell lymphoma . Some IOL present as ocular involvement of previously diagnosed or simultaneous central nervous system (CNS) lymphoma, and others present as isolated ocular lymphoma without evidence of CNS disease, termed primary intraocular lymphoma (PIOL).…”

Regulation of development and cancer by the R2B subfamily of RPTPs and the implications of proteolysis

“…Loss of heterozygosity in the PTPRK coding region on chromosome 6 is associated with malignant glioma [76], central nervous system lymphomas [77], primary intraocular lymphoma [78], and pancreatic cancers [79]. The PTPRK gene is mutated in HNSCC [67], and a mutated PTPκ was identified as a melanoma antigen on CD4 + T-cells [80].…”

“…Low levels of PTPκ transcripts are observed in breast cancer tissue [85] and in 20% of melanoma cells and tissue biopsies [86]. The consensus is that PTPκ is a tumor suppressor, as reduced PTPκ expression is correlated with shorter disease free-survival times in breast cancer [85], and loss of heterozygosity of the PTPRK region of chromosome 6 is associated with shorter patient survival with CNS lymphoma and primary ocular lymphoma [77, 78]. In at least one instance, however, PTPκ has a hypothesized oncogenic function as an inhibitor of apoptosis [87].…”