title: Genome-Wide Analysis of Ocular Adnexal Lymphoproliferative Disorders Using High-Resolution Single Nucleotide Polymorphism Array.
abstract: OBJECTIVE
  We identified the genomic signature of ocular adnexal lymphoproliferative disorders (LPDs), especially ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma, IgG4-related ophthalmic disease (IgG4-ROD), reactive lymphoid hyperplasia (RLH), and diffuse large B-cell lymphoma (DLBCL).
  
  
  METHODS
  We included 52 subjects with ocular adnexal LPDs (13 orbital MALT lymphomas, 16 conjunctival MALT lymphomas, 13 IgG4-RODs, 4 RLHs, and 6 DLBCLs) who had been treated at the Tokyo Medical University Hospital from 2008 to 2012. Genomic DNA was extracted from the tumor tissues and subjected to high-resolution single nucleotide polymorphism array (SNP-A) karyotyping using GeneChip Human Mapping 250K SNP arrays. The array data were investigated using Copy Number Analysis for GeneChips (CNAG) software.
  
  
  RESULTS
  In ocular adnexal MALT lymphomas, the most frequent copy number (CN) gain region was trisomy 3 detected in 31% (9/29), followed by trisomy 18 in 17% (5/29), and 6p and 21q in 14% (4/29). The most frequent CN loss regions were 6q and 9p, detected in 7% (2/29). Uniparental disomy was detected on 6q in 14% (4/29), followed by 3q in 10% (3/29). Copy number variations (CNVs) were not detected in IgG4-RODs and RLHs. Conversely, CNVs were more frequent in DLBCLs than in ocular adnexal MALT lymphomas. Copy number variations were detected in 77% (10/13) of orbital MALT lymphomas and in 67% (11/16) of conjunctival MALT lymphomas.
  
  
  CONCLUSIONS
  High-resolution single nucleotide polymorphism array is a useful method for discriminating ocular adnexal lymphomas from benign LPDs. The differences in the chromosomal abnormality patterns may reflect the activity of ocular adnexal LPDs.
authors.affiliation: Department of Ophthalmology Tokyo Medical University, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Ophthalmology Tokyo Medical University, Tokyo, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.affiliation: Department of Ophthalmology Tokyo Medical University, Tokyo, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Department of Ophthalmology Tokyo Medical University, Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamakawa
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sato-Otsubo
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Ophthalmology Tokyo Medical University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056915:DNA Copy Number Variations; D005134:Eye Neoplasms / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019310:Pseudolymphoma / Q000235:genetics*; D055815:Young Adult