Uniparental disomies, homozygous deletions, amplifications, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profiling.


:Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. However, only a limited number of target genes have been identified. We have studied 10 MCL cell lines and 28 primary tumors with a combination of a high-density single-nucleotide polymorphism array and gene expression profiling. We detected highly altered genomes in the majority of the samples with a high number of partial uniparental disomies (UPDs). The UPD at 17p was one of the most common, and it was associated with TP53 gene inactivation. Homozygous deletions targeted 4 known tumor suppressor genes (CDKN2C, BCL2L11, CDKN2A, and RB1) and 6 new genes (FAF1, MAP2, SP100, MOBKL2B, ZNF280A, and PRAME). Gene amplification coupled with overexpression was identified in 35 different regions. The most recurrent amplified regions were 11q13.3-q13.5, 13q31.3, and 18q21.33, which targeted CCND1, C13orf25, and BCL2, respectively. Interestingly, the breakpoints flanking all the genomic alterations, including UPDs, were significantly associated with genomic regions enriched in copy number variants and segmental duplications, suggesting that the recombination at these regions may play a role in the genomic instability of MCL. This integrative genomic analysis has revealed target genes that may be potentially relevant in MCL pathogenesis.






Beà S,Salaverria I,Armengol L,Pinyol M,Fernández V,Hartmann EM,Jares P,Amador V,Hernández L,Navarro A,Ott G,Rosenwald A,Estivill X,Campo E




Has Abstract


2009-03-26 00:00:00
















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    abstract::Follicular dendritic cells (FDCs) form a reticular FDC network in the lymphoid follicle that is essential for the retention and presentation of native antigens in the form of antigen-antibody immune complexes (ICs) to B cells during secondary immune response. Although the presence of migrating precursors of FDCs has b...


    pub_type: 杂志文章


    authors: Murakami T,Chen X,Hase K,Sakamoto A,Nishigaki C,Ohno H

    更新日期:2007-08-15 00:00:00

  • Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire.

    abstract::The human peripheral B-cell compartment displays a large population of immunoglobulin M-positive, immunoglobulin D-positive CD27(+) (IgM(+)IgD(+)CD27(+)) "memory" B cells carrying a mutated immunoglobulin receptor. By means of phenotypic analysis, complementarity-determining region 3 (CDR3) spectratyping during a T-in...


    pub_type: 杂志文章


    authors: Weller S,Braun MC,Tan BK,Rosenwald A,Cordier C,Conley ME,Plebani A,Kumararatne DS,Bonnet D,Tournilhac O,Tchernia G,Steiniger B,Staudt LM,Casanova JL,Reynaud CA,Weill JC

    更新日期:2004-12-01 00:00:00

  • Mast cell-derived TNF can promote Th17 cell-dependent neutrophil recruitment in ovalbumin-challenged OTII mice.

    abstract::Both mast cells and IL-17 can contribute to host defense and pathology in part by orchestrating neutrophil recruitment, but the possible role of mast cells in IL-17-induced inflammation remains to be defined. We found that mast cells and IL-17, but neither IFN-gamma nor FcRgamma signaling, contributed significantly to...


    pub_type: 杂志文章


    authors: Nakae S,Suto H,Berry GJ,Galli SJ

    更新日期:2007-05-01 00:00:00

  • The human cardiac mast cell: localization, isolation, phenotype, and functional characterization.

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    pub_type: 杂志文章


    authors: Sperr WR,Bankl HC,Mundigler G,Klappacher G,Grossschmidt K,Agis H,Simon P,Laufer P,Imhof M,Radaszkiewicz T,Glogar D,Lechner K,Valent P

    更新日期:1994-12-01 00:00:00

  • Therapy of severe aplastic anemia in young adults and children with allogeneic bone marrow transplantation.

    abstract::During an 8-year period, 28 young adults (median age 27 years) and 30 children (median age 10 years) with severe aplastic anemia have received allogeneic bone marrow transplantation (BMT) from major histocompatibility locimatched sibling donors after preparation with cyclophosphamide and total lymphoid irradiation (TL...


    pub_type: 杂志文章


    authors: McGlave PB,Haake R,Miller W,Kim T,Kersey J,Ramsay NK

    更新日期:1987-11-01 00:00:00

  • A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels.

    abstract::Plasma factor VIII coagulant activity (FVIII:C) level is a highly heritable quantitative trait that is strongly correlated with thrombosis risk. Polymorphisms within only 1 gene, the ABO blood-group locus, have been unequivocally demonstrated to contribute to the broad population variability observed for this trait. B...


    pub_type: 临床试验,杂志文章,多中心研究


    authors: Viel KR,Machiah DK,Warren DM,Khachidze M,Buil A,Fernstrom K,Souto JC,Peralta JM,Smith T,Blangero J,Porter S,Warren ST,Fontcuberta J,Soria JM,Flanders WD,Almasy L,Howard TE

    更新日期:2007-05-01 00:00:00

  • The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL).

    abstract::We document findings on c-kit (CD117) expression in 1,937 pediatric and adult de novo acute leukemia cases, diagnosed in five single European centers. All cases were well characterized as to the morphologic, cytochemical, and immunologic features, according to the European Group for the Immunological Classification of...


    pub_type: 杂志文章


    authors: Bene MC,Bernier M,Casasnovas RO,Castoldi G,Knapp W,Lanza F,Ludwig WD,Matutes E,Orfao A,Sperling C,van't Veer MB

    更新日期:1998-07-15 00:00:00

  • Cytokine-induced inside-out activation of FcalphaR (CD89) is mediated by a single serine residue (S263) in the intracellular domain of the receptor.

    abstract::Fc receptors play an important role in leukocyte activation and the modulation of ligand binding ("activation") is a critical point of regulation. Previous studies demonstrated that the Fc receptor for IgA (FcalphaRI/CD89) is regulated by cytokine stimulation, switching it to a high-binding state. To investigate the m...


    pub_type: 杂志文章


    authors: Bracke M,Lammers JW,Coffer PJ,Koenderman L

    更新日期:2001-06-01 00:00:00

  • A novel mutation in the coding sequence of the FY*B allele of the Duffy chemokine receptor gene is associated with an altered erythrocyte phenotype.

    abstract::The Duffy blood group system is of clinical and biological significance. Antibodies to Duffy antigens are responsible for some cases of transfusion incompatibility and newborn hemolytic disease. The Duffy protein is a receptor for the Plasmodium vivax erythrocyte-binding protein and is also a receptor for various chem...


    pub_type: 杂志文章


    authors: Parasol N,Reid M,Rios M,Castilho L,Harari I,Kosower NS

    更新日期:1998-10-01 00:00:00

  • Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway.

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    pub_type: 杂志文章


    authors: Chin H,Arai A,Wakao H,Kamiyama R,Miyasaka N,Miura O

    更新日期:1998-05-15 00:00:00

  • Induction of megakaryocytopoiesis and thrombocytopoiesis by JTZ-132, a novel small molecule with thrombopoietin mimetic activities.

    abstract::We report in this paper that a novel small molecule, JTZ-132, induced growth and differentiation of megakaryocytic progenitor cells and improved thrombocytopenia in myelosuppressed mice. JTZ-132 stimulated proliferation of UT-7/TPO cells, a cell line highly sensitive to thrombopoietin (TPO), and exhibited full efficac...


    pub_type: 杂志文章


    authors: Inagaki K,Oda T,Naka Y,Shinkai H,Komatsu N,Iwamura H

    更新日期:2004-07-01 00:00:00

  • The significance of bcr-abl molecular detection in chronic myeloid leukemia patients "late," 18 months or more after transplantation.

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    pub_type: 临床试验,杂志文章


    authors: Radich JP,Gooley T,Bryant E,Chauncey T,Clift R,Beppu L,Edmands S,Flowers ME,Kerkof K,Nelson R,Appelbaum FR

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  • Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization.

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    pub_type: 杂志文章


    authors: Stratman AN,Schwindt AE,Malotte KM,Davis GE

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    authors: Ohwada A,Rafii S,Moore MA,Crystal RG

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  • Antilymphocytic antibodies and marrow transplantation. XII. Suppression of graft-versus-host disease by T-cell-modulating and depleting antimouse CD3 antibody is most effective when preinjected in the marrow recipient.

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    authors: Mysliwietz J,Thierfelder S

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  • Clonal competition with alternating dominance in multiple myeloma.

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    authors: Keats JJ,Chesi M,Egan JB,Garbitt VM,Palmer SE,Braggio E,Van Wier S,Blackburn PR,Baker AS,Dispenzieri A,Kumar S,Rajkumar SV,Carpten JD,Barrett M,Fonseca R,Stewart AK,Bergsagel PL

    更新日期:2012-08-02 00:00:00

  • Essential role for ICSBP in the in vivo development of murine CD8alpha + dendritic cells.

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    authors: Aliberti J,Schulz O,Pennington DJ,Tsujimura H,Reis e Sousa C,Ozato K,Sher A

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  • MicroRNA regulation of STAT4 protein expression: rapid and sensitive modulation of IL-12 signaling in human natural killer cells.

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    pub_type: 杂志文章


    authors: Huang Y,Lei Y,Zhang H,Hou L,Zhang M,Dayton AI

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  • Epstein-Barr virus infection precedes clonal expansion in Burkitt's and acquired immunodeficiency syndrome-associated lymphoma.

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    authors: Neri A,Barriga F,Inghirami G,Knowles DM,Neequaye J,Magrath IT,Dalla-Favera R

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  • Extracellular ubiquitin inhibits the TNF-alpha response to endotoxin in peripheral blood mononuclear cells and regulates endotoxin hyporesponsiveness in critical illness.

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    authors: Majetschak M,Krehmeier U,Bardenheuer M,Denz C,Quintel M,Voggenreiter G,Obertacke U

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  • CXCL12 expression by invasive trophoblasts induces the specific migration of CD16- human natural killer cells.

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  • Circulating endothelial-cell kinetics and viability predict survival in breast cancer patients receiving metronomic chemotherapy.

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    pub_type: 杂志文章,随机对照试验


    authors: Mancuso P,Colleoni M,Calleri A,Orlando L,Maisonneuve P,Pruneri G,Agliano A,Goldhirsch A,Shaked Y,Kerbel RS,Bertolini F

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  • Reciprocal expression of CD38 and CD34 by adult murine hematopoietic stem cells.

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    pub_type: 杂志文章


    authors: Tajima F,Deguchi T,Laver JH,Zeng H,Ogawa M

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  • Characteristics and outcomes of patients with chronic myeloid leukemia and T315I mutation following failure of imatinib mesylate therapy.

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    authors: Jabbour E,Kantarjian H,Jones D,Breeden M,Garcia-Manero G,O'Brien S,Ravandi F,Borthakur G,Cortes J

    更新日期:2008-07-01 00:00:00

  • Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease.

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    authors: Camus SM,De Moraes JA,Bonnin P,Abbyad P,Le Jeune S,Lionnet F,Loufrani L,Grimaud L,Lambry JC,Charue D,Kiger L,Renard JM,Larroque C,Le Clésiau H,Tedgui A,Bruneval P,Barja-Fidalgo C,Alexandrou A,Tharaux PL,Boulanger CM

    更新日期:2015-06-11 00:00:00

  • Attachment of the PSGL-1 cytoplasmic domain to the actin cytoskeleton is essential for leukocyte rolling on P-selectin.

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    pub_type: 杂志文章


    authors: Snapp KR,Heitzig CE,Kansas GS

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  • Structural basis for quinine-dependent antibody binding to platelet integrin αIIbβ3.

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    pub_type: 杂志文章


    authors: Zhu J,Zhu J,Bougie DW,Aster RH,Springer TA

    更新日期:2015-10-29 00:00:00

  • STIM1 is essential for Fcgamma receptor activation and autoimmune inflammation.

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    pub_type: 杂志文章


    authors: Braun A,Gessner JE,Varga-Szabo D,Syed SN,Konrad S,Stegner D,Vögtle T,Schmidt RE,Nieswandt B

    更新日期:2009-01-29 00:00:00

  • Detection of the t(2;5)(p23;q35) and NPM-ALK fusion in non-Hodgkin's lymphoma by two-color fluorescence in situ hybridization.

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    pub_type: 杂志文章


    authors: Mathew P,Sanger WG,Weisenburger DD,Valentine M,Valentine V,Pickering D,Higgins C,Hess M,Cui X,Srivastava DK,Morris SW

    更新日期:1997-03-01 00:00:00

  • Causal relationship between hyperfibrinogenemia, thrombosis, and resistance to thrombolysis in mice.

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    pub_type: 杂志文章


    authors: Machlus KR,Cardenas JC,Church FC,Wolberg AS

    更新日期:2011-05-05 00:00:00