title: Deletion or epigenetic silencing of AJAP1 on 1p36 in glioblastoma.
abstract: Glioblastoma is universally fatal because of its propensity for rapid recurrence due to highly migratory tumor cells. Unraveling the genomic complexity that underlies this migratory characteristic could provide therapeutic targets that would greatly complement current surgical therapy. Using multiple high-resolution genomic screening methods, we identified a single locus, adherens junctional associated protein 1 (AJAP1) on chromosome 1p36 that is lost or epigenetically silenced in many glioblastomas. We found AJAP1 expression absent or reduced in 86% and 100% of primary glioblastoma tumors and cell lines, respectively, and the loss of expression correlates with AJAP1 methylation. Restoration of AJAP1 gene expression by transfection or demethylation agents results in decreased tumor cell migration in glioblastoma cell lines. This work shows the significant loss of expression of AJAP1 in glioblastoma and provides evidence of its role in the highly migratory characteristic of these tumors.
authors.affiliation: Department of Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China.
authors.forename: Ningjing
authors.initials: N
authors.lastname: Lin
authors.forename: Chunhui
authors.initials: C
authors.lastname: Di
authors.forename: Kathy
authors.initials: K
authors.lastname: Bortoff
authors.forename: Jinrong
authors.initials: J
authors.lastname: Fu
authors.forename: Peter
authors.initials: P
authors.lastname: Truszkowski
authors.forename: Patrick
authors.initials: P
authors.lastname: Killela
authors.forename: Chris
authors.initials: C
authors.lastname: Duncan
authors.forename: Roger
authors.initials: R
authors.lastname: McLendon
authors.forename: Darell
authors.initials: D
authors.lastname: Bigner
authors.forename: Simon
authors.initials: S
authors.lastname: Gregory
authors.forename: David Cory
authors.initials: DC
authors.lastname: Adamson
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D034741:RNA, Small Interfering
chemical_list: C483313:AJAP1 protein, human; D015815:Cell Adhesion Molecules; D034741:RNA, Small Interfering; D000077209:Decitabine; D001374:Azacitidine