title: Multigene methylation analysis of ocular adnexal MALT lymphoma and their relationship to Chlamydophila psittaci infection and clinical characteristics in South Korea.
abstract: OBJECTIVE
  We investigated the aberrant promoter methylation status of known or suspected tumor suppressor genes in ocular adnexal lymphoma (OAL) and the possible association with clinical characteristics and Chlamydophila psittaci infection.
  
  
  METHODS
  Thirty-five cases of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma cases were examined for the methylation status of nine genes using methylation-specific PCR and for the detection of C. psittaci DNA using PCR. The medical records were reviewed retrospectively. Patient demographics, clinical characteristics including the response of the lymphoma to the therapy, and C. psittaci infection status were evaluated for possible association with methylation frequencies.
  
  
  RESULTS
  CpG island methylation in nine genes was variously found as follows; DAPK (94.3%), ECAD (77.1%), MT1G (48.6%), THBS1 (37.1%), RAR-β (31.4%), p16 (20%), MGMT (5.7%), p14 (0%), and RASSF1A (0%). Methylation was not observed in any of 13 control cases. C. psittaci DNA was observed in 25 (75.8%) of 33 patients with available tumor tissues, and ECAD hypermethylation was significantly higher in C. psittaci-positive cases (P = 0.041). Promoter hypermethylation status was not correlated with clinical characteristics.
  
  
  CONCLUSIONS
  Aberrant CpG island methylation of tumor suppressor genes is a frequent event in ocular adnexal MALT lymphoma. In particular, high frequencies of DAPK and ECAD methylation may be strongly correlated with ocular adnexal MALT lymphomagenesis in South Korea. Furthermore, ECAD hypermethylation is closely associated with C. psittaci infection, which may shed light on the mechanisms of bacterium-induced oncogenesis.
authors.affiliation: Department of Ophthalmology, Seoul National University Boramae Hospital, Seoul, Republic of Korea.
authors.forename: Ho-Kyung
authors.initials: HK
authors.lastname: Choung
authors.forename: Young A
authors.initials: YA
authors.lastname: Kim
authors.forename: Min Joung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Namju
authors.initials: N
authors.lastname: Kim
authors.forename: Sang In
authors.initials: SI
authors.lastname: Khwarg
mesh_terms: D002691:Chlamydophila psittaci; D019175:DNA Methylation; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D005134:Eye Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D018442:Lymphoma, B-Cell, Marginal Zone / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D009956:Psittacosis / Q000150:complications* / Q000382:microbiology; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D004269:DNA, Bacterial; D004273:DNA, Neoplasm