title: Integrative analysis reveals 53BP1 copy loss and decreased expression in a subset of human diffuse large B-cell lymphomas.
abstract: p53-Binding protein 1 (53BP1) encodes a critical checkpoint protein that localizes to sites of DNA double-strand breaks (DSBs) and participates in DSB repair. Mice that are 53bp1 deficient or hemizygous have an increased incidence of lymphoid malignancies. However, 53BP1 abnormalities in primary human tumors have not been described. By combining high-density single nucleotide polymorphism (HD SNP) array data and gene expression profiles, we found 9 of 63 newly diagnosed human diffuse large B-cell lymphomas (DLBCLs) with single copy loss of the chromosome 15q15 region including the 53BP1 locus; these nine tumors also had significantly lower levels of 53BP1 transcripts. 53BP1 single copy loss found with the HD SNP array platform was subsequently confirmed by fluorescence in situ hybridization. These studies highlight the role of 53BP1 copy loss in primary human DLBCLs and the value of integrative analyses in detecting this genetic lesion in human tumors.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Takeyama
authors.forename: S
authors.initials: S
authors.lastname: Monti
authors.forename: J P
authors.initials: JP
authors.lastname: Manis
authors.forename: P
authors.initials: P
authors.lastname: Dal Cin
authors.forename: G
authors.initials: G
authors.lastname: Getz
authors.forename: R
authors.initials: R
authors.lastname: Beroukhim
authors.forename: S
authors.initials: S
authors.lastname: Dutt
authors.forename: J C
authors.initials: JC
authors.lastname: Aster
authors.forename: F W
authors.initials: FW
authors.lastname: Alt
authors.forename: T R
authors.initials: TR
authors.lastname: Golub
authors.forename: M A
authors.initials: MA
authors.lastname: Shipp
mesh_terms: D000483:Alleles; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1