title: Epigenetic changes and their clinical relevance in Saudi diffuse large B-cell lymphoma. A molecular and tissue microarray analysis of 100 cases.
abstract: OBJECTIVE
  The gene encoding the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is transcriptionally silenced by promoter hypermethylation in several human cancers including diffuse large B-cell lymphoma (DLBCL). We explored the aberrant promoter methylation of MGMT in Saudi diffuse large B-cell lymphoma and to investigate MGMT hypermethylation has an effect on patient's overall survival.
  
  
  METHODS
  In a retrospective cohort study, 100 cases of DLBCL were collected from the Department of Pathology at King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia. We used methylation specific polymerase chain reaction to analyze the MGMT promoter methylation status in 100 tumor DNA of Saudi DLBCL patients receiving multi drug regimens. Tissue microarray (TMA) of these cases was also constructed. The MGMT protein expression was analyzed immunohistochemically. Molecular data were correlated with clinical outcome.
  
  
  RESULTS
  Seventy one percent (71%) of 100 DLBCL patients showed MGMT promoter hypermethylation in their lymphoma. The presence of MGMT methylation was associated with statistically significant increase in the overall survival (p=0.02). The MGMT promoter hypermethylation was independent and a strong prognostic factor.
  
  
  CONCLUSIONS
  The MGMT promoter hypermethylation appears to be useful marker for predicting survival in patient with DLBCL treated with multi drug regimens including cyclophosphamide, at the same time the study shows that TMA technology is useful for immunohistochemical analysis of large lymphoma populations.
authors.affiliation: Research Centre, King Faisal Specialist Hospital, MBC 98-16, PO Box 3354, Riyadh 11211, Kingdom of Saudi Arabia. kkuraya@kfshrc.edu.sa
authors.forename: Khawla S
authors.initials: KS
authors.lastname: Al-Kuraya
authors.forename: Abdul K
authors.initials: AK
authors.lastname: Siraj
authors.forename: Fouad A
authors.initials: FA
authors.lastname: Al-Dayel
authors.forename: Adnan A
authors.initials: AA
authors.lastname: Ezzat
authors.forename: Naif A
authors.initials: NA
authors.lastname: Al-Jommah
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Atizado
authors.forename: Rajeswari N
authors.initials: RN
authors.lastname: Narayanappa
mesh_terms: D015331:Cohort Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D012529:Saudi Arabia; D015996:Survival Rate
chemical_list: D019853:O(6)-Methylguanine-DNA Methyltransferase