title: BOB.1-positive Classical Hodgkin's Lymphoma Carries Hypermethylation of Its Promoter as Epigenetic Marker of Gene-silencing Memory.
abstract: Analysis of archival formalin-fixed, paraffin-embedded (FFPE) pathological specimens of three case of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) and three cases of classical Hodgkin lymphoma (CHL) revealed that hypermethylation of the BOB.1 gene promoter was exclusively observed in CHL. A discrepancy was observed, however, between the methylation status of the BOB.1 gene promoter and its expression in the EBV-positive mixed cellular CHL (MCCHL). Since MCCHL lacks the typical B-cell phenotype even in the presence of abundant BOB.1 transcription factors, functional activity of BOB.1 may be lost or reduced by a mechanism other than epigenetic gene silencing. When some tumor-suppressor gene products have lost their biological function, impact or significance of derepression of such genes may be little. Therefore, when interpreting immunohistochemical results for diagnostic or research purposes, it must be borne in mind that apparent positive immunostaining can merely be the result of chromatin remodeling and that such transient expression often has little functional significance. Any apparent positive immunohistochemical result needs to be interpreted carefully with the help of the hypermethylation status as a molecular marker of gene silencing memory.
authors.affiliation: Department of Molecular Pathology, Ehime University Graduate School of Medicine , Shitsukawa, Toon City, Ehime 791-0295, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Molecular Pathology, Ehime University Graduate School of Medicine , Shitsukawa, Toon City, Ehime 791-0295, Japan.
authors.forename: Riko
authors.initials: R
authors.lastname: Kitazawa
authors.affiliation: Department of Molecular Pathology, Ehime University Graduate School of Medicine , Shitsukawa, Toon City, Ehime 791-0295, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Mizuno
authors.affiliation: Department of Molecular Pathology, Ehime University Graduate School of Medicine , Shitsukawa, Toon City, Ehime 791-0295, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Kuwahara
authors.affiliation: Department of Molecular Pathology, Ehime University Graduate School of Medicine , Shitsukawa, Toon City, Ehime 791-0295, Japan.
authors.forename: Chizu
authors.initials: C
authors.lastname: Ito
authors.affiliation: Department of Molecular Pathology, Ehime University Graduate School of Medicine , Shitsukawa, Toon City, Ehime 791-0295, Japan.
authors.forename: Atsuro
authors.initials: A
authors.lastname: Sugita
authors.affiliation: Department of Molecular Pathology, Ehime University Graduate School of Medicine , Shitsukawa, Toon City, Ehime 791-0295, Japan.
authors.forename: Ryuma
authors.initials: R
authors.lastname: Haraguchi
authors.affiliation: Department of Molecular Pathology, Ehime University Graduate School of Medicine , Shitsukawa, Toon City, Ehime 791-0295, Japan.
authors.forename: Sohei
authors.initials: S
authors.lastname: Kitazawa
keywords: Hodgkin’s disease; methylation; microdissection; transcription factor