title: High throughput tissue microarray analysis of FHIT expression in diffuse large cell B-cell lymphoma from Saudi Arabia.
abstract: Recent studies have suggested a potential prognostic role of alterations of the fragile histidine triad (FHIT) gene in diffuse large B-cell lymphoma. To evaluate possible mechanisms of FHIT inactivation and to further clarify its potential prognostic relevance, we analyzed a set of 114 diffuse large B-cell lymphoma with clinical follow-up information. Tissue microarrays were analyzed by immunohistochemistry for protein expression, and corresponding DNA samples were analyzed for FHIT promotor hypermethlyation. Reduced or absent FHIT expression was found in 75 of 114 diffuse large B-cell lymphoma (66%), but was unrelated to clinical tumor stage or patient prognosis. FHIT promotor hypermethylation was observed in 29 of 93 (23%) interpretable diffuse large B-cell lymphoma. Hypermethylation was not significantly correlated to protein expression loss, which could be explained by competing mechanisms for FHIT inactivation in a substantial fraction of non FHIT hypermethylated diffuse large B-cell lymphoma. Hypermethylation was significantly associated with poor prognosis of diffuse large B-cell lymphoma patients and predominantly seen in nongerminal center diffuse large B-cell lymphoma (27%), but less frequent (13%) in germinal center diffuse large B-cell lymphoma. In summary, these data suggest that promotor hypermethylation is responsible for reduced FHIT expression in a substantial subset of diffuse large B-cell lymphoma, which is primarily composed of nongerminal center subtype with poor patient prognosis.
authors.affiliation: Cancer Genomics, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Khawla
authors.initials: K
authors.lastname: Al Kuraya
authors.forename: Abdul Khalid
authors.initials: AK
authors.lastname: Siraj
authors.forename: Prashant
authors.initials: P
authors.lastname: Bavi
authors.forename: Naif
authors.initials: N
authors.lastname: Al-Jomah
authors.forename: Hassan
authors.initials: H
authors.lastname: El-Solh
authors.forename: Adnan
authors.initials: A
authors.lastname: Ezzat
authors.forename: Fouad
authors.initials: F
authors.lastname: Al-Dayel
authors.forename: Asim
authors.initials: A
authors.lastname: Belgaumi
authors.forename: Amani
authors.initials: A
authors.lastname: Al-Kofide
authors.forename: Rajeh
authors.initials: R
authors.lastname: Sabbah
authors.forename: Salwa
authors.initials: S
authors.lastname: Sheikh
authors.forename: Samir
authors.initials: S
authors.lastname: Amr
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012529:Saudi Arabia; D015996:Survival Rate; D046888:Tissue Array Analysis / Q000379:methods*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase