title: Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia.
abstract: DNA methylation is associated with malignant transformation, but limitations imposed by genetic variability, tumor heterogeneity, availability of paired normal tissues and methodologies for global assessment of DNA methylation have limited progress in understanding the extent of epigenetic events in the initiation and progression of human cancer and in identifying genes that undergo methylation during cancer. We developed a mouse model of T/natural killer acute lymphoblastic leukemia that is always preceded by polyclonal lymphocyte expansion to determine how aberrant promoter DNA methylation and consequent gene silencing might be contributing to leukemic transformation. We used restriction landmark genomic scanning with this mouse model of preleukemia reproducibly progressing to leukemia to show that specific genomic methylation is associated with only the leukemic phase and is not random. We also identified Idb4 as a putative tumor-suppressor gene that is methylated in most mouse and human leukemias but in only a minority of other human cancers.
authors.affiliation: Internal Medicine, Division of Hematology/Oncology, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Chunhui
authors.initials: C
authors.lastname: Liu
authors.forename: Jeff
authors.initials: J
authors.lastname: Vandeusen
authors.forename: Brian
authors.initials: B
authors.lastname: Becknell
authors.forename: Zunyan
authors.initials: Z
authors.lastname: Dai
authors.forename: Yue-Zhong
authors.initials: YZ
authors.lastname: Wu
authors.forename: Aparna
authors.initials: A
authors.lastname: Raval
authors.forename: Te-Hui
authors.initials: TH
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Charlene
authors.initials: C
authors.lastname: Mao
authors.forename: Shujun
authors.initials: S
authors.lastname: Liu
authors.forename: Laura T
authors.initials: LT
authors.lastname: Smith
authors.forename: Stephen
authors.initials: S
authors.lastname: Lee
authors.forename: Laura
authors.initials: L
authors.lastname: Rassenti
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: John
authors.initials: J
authors.lastname: Byrd
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D051796:Inhibitor of Differentiation Proteins; D007938:Leukemia / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C086479:Idb4 protein, mouse; D051796:Inhibitor of Differentiation Proteins; D014157:Transcription Factors