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

Cancer Sci. 2014 May;105(5):592-9. doi: 10.1111/cas.12388. Epub 2014 Apr 1.

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.

Keywords: Central nervous system; IL-10; intraocular lymphoma; single nucleotide polymorphism; vitreous body.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Central Nervous System Neoplasms / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Female
  • Gene Deletion
  • Gene Dosage / genetics*
  • Humans
  • Interleukin-10 / genetics
  • Intraocular Lymphoma / genetics*
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • IL10 protein, human
  • Interleukin-10
  • PTPRK protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2