title: Genome-wide DNA methylation profiles according to Chlamydophila psittaci infection and the response to doxycycline treatment in ocular adnexal lymphoma.
abstract: OBJECTIVE
  To compare genome-wide DNA methylation profiles according to Chlamydophila psittaci (Cp) infection status and the response to doxycycline treatment in Korean patients with ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL).
  
  
  METHODS
  Twelve ocular adnexal EMZL cases were classified into two groups (six Cp-positive cases and six Cp-negative cases). Among the 12 cases, eight were treated with doxycycline as first-line therapy, and they were divided into two groups according to their response to the treatment (four doxy-responders and four doxy-nonresponders). The differences in the DNA methylation states of 27,578 methylation sites in 14,000 genes were evaluated using Illumina bead assay technology. We also validated the top-ranking differentially methylated genes (DMGs) with bisulfite direct sequencing or pyrosequencing.
  
  
  RESULTS
  The Infinium methylation chip assay revealed 180 DMGs in the Cp-positive group (74 hypermethylated genes and 106 hypomethylated genes) compared to the Cp-negative group. Among the 180 DMGs, DUSP22, which had two significantly hypomethylated loci, was validated, and the correlation was significant for one CpG site (Spearman coefficient=0.6478, p=0.0262). Regarding the response to doxycycline treatment, a total of 778 DMGs were revealed (389 hypermethylated genes and 336 hypomethylated genes in the doxy-responder group). In a subsequent replication study for representative hypomethylated (IRAK1) and hypermethylated (CXCL6) genes, the correlation between the bead chip analysis and pyrosequencing was significant (Spearman coefficient=0.8961 and 0.7619, respectively, p<0.05).
  
  
  CONCLUSIONS
  Ocular adnexal EMZL showed distinct methylation patterns according to Cp infection and the response to doxycycline treatment in this genome-wide methylation study. Among the candidate genes, DUSP22 has a methylation status that was likely attributable to Cp infection. Our data also suggest that the methylation statuses of IRAK1 and CXCL6 may reflect the response to doxycycline treatment.
authors: Department of Ophthalmology, College of Medicine, Seoul National University, Seoul Korea ; Department of Ophthalmology, Hallym University Sacred Heart Hospital, Anyang, Korea.
authors: Min Joung
authors: MJ
authors: Lee
authors: Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea.
authors: Byung-Joo
authors: BJ
authors: Min
authors: Department of Ophthalmology, College of Medicine, Seoul National University, Seoul Korea ; Department of Ophthalmology, Seoul National University Boramae Hospital, Seoul, Korea.
authors: Ho-Kyung
authors: HK
authors: Choung
authors: Department of Ophthalmology, College of Medicine, Seoul National University, Seoul Korea ; Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Namju
authors: N
authors: Kim
authors: Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea.
authors: Young A
authors: YA
authors: Kim
authors: Department of Ophthalmology, College of Medicine, Seoul National University, Seoul Korea ; Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea.
authors: Sang In
authors: SI
authors: Khwarg
mesh_terms: D000328:Adult; D000368:Aged; D002691:Chlamydophila psittaci / Q000187:drug effects / Q000502:physiology*; D016000:Cluster Analysis; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use*; D005134:Eye Neoplasms / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009956:Psittacosis / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA
chemical_list: D004269:DNA, Bacterial; D004318:Doxycycline