genetic translocation


Summary: A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.

Top Publications

  1. ncbi The impact of translocations and gene fusions on cancer causation
    Felix Mitelman
    Lund University, Department of Clinical Genetics, Lund University Hospital, SE 221 85 Lund, Sweden
    Nat Rev Cancer 7:233-45. 2007
  2. ncbi Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites
    Francene J Lemoine
    Department of Biology and Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Cell 120:587-98. 2005
  3. ncbi Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
    S E Artandi
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 406:641-5. 2000
  4. pmc Reciprocal translocations in Saccharomyces cerevisiae formed by nonhomologous end joining
    Xin Yu
    Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA
    Genetics 166:741-51. 2004
  5. ncbi A novel gene family NBPF: intricate structure generated by gene duplications during primate evolution
    Karl Vandepoele
    Department for Molecular Biomedical Research, VIB Ghent University, Ghent, Belgium
    Mol Biol Evol 22:2265-74. 2005
  6. ncbi Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12)
    Y Kuno
    First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
    Blood 97:1050-5. 2001
  7. ncbi The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25
    M Ladanyi
    Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Oncogene 20:48-57. 2001
  8. pmc Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication
    Elena V Linardopoulou
    Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North C3 168, Seattle, Washington 98109, USA
    Nature 437:94-100. 2005
  9. ncbi Chromosome translocations in multiple myeloma
    P L Bergsagel
    Department of Medicine, Division of Hematology and Oncology, Weill Medical College of Cornell University, New York, NY, USA
    Oncogene 20:5611-22. 2001
  10. pmc The neurobeachin gene is disrupted by a translocation in a patient with idiopathic autism
    D Castermans
    J Med Genet 40:352-6. 2003

Detail Information

Publications300 found, 100 shown here

  1. ncbi The impact of translocations and gene fusions on cancer causation
    Felix Mitelman
    Lund University, Department of Clinical Genetics, Lund University Hospital, SE 221 85 Lund, Sweden
    Nat Rev Cancer 7:233-45. 2007
    ..With the advent of new and powerful investigative tools that enable the detection of cytogenetically cryptic rearrangements, this proportion is likely to increase substantially...
  2. ncbi Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites
    Francene J Lemoine
    Department of Biology and Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Cell 120:587-98. 2005
    ..We demonstrate that this pair of Ty elements constitutes a preferred site for double-strand DNA breaks when DNA replication is compromised, analogous to the fragile sites observed in mammalian chromosomes...
  3. ncbi Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
    S E Artandi
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 406:641-5. 2000
    ..Our data suggest a model in which telomere dysfunction brought about by continual epithelial renewal during life generates the massive ploidy changes associated with the development of epithelial cancers...
  4. pmc Reciprocal translocations in Saccharomyces cerevisiae formed by nonhomologous end joining
    Xin Yu
    Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA
    Genetics 166:741-51. 2004
    ..In some cases the translocation partner is formed by a break at a cryptic HO recognition site. Our results demonstrate that NHEJ-mediated reciprocal translocations can form in S. cerevisiae as a consequence of DSB repair...
  5. ncbi A novel gene family NBPF: intricate structure generated by gene duplications during primate evolution
    Karl Vandepoele
    Department for Molecular Biomedical Research, VIB Ghent University, Ghent, Belgium
    Mol Biol Evol 22:2265-74. 2005
    ..Overall, this novel NBPF family reflects the continuous evolution of primate genomes that resulted in large physiological differences, and its potential role in this process is discussed...
  6. ncbi Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12)
    Y Kuno
    First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
    Blood 97:1050-5. 2001
    ..TEL-Syk is a novel transforming protein and leads to the transformation of hematopoietic cells. These data implicate that the rearranged Syk gene is involved in the pathogenesis of hematopoietic malignancies...
  7. ncbi The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25
    M Ladanyi
    Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Oncogene 20:48-57. 2001
    ..Oncogene (2001) 20, 48 - 57...
  8. pmc Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication
    Elena V Linardopoulou
    Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North C3 168, Seattle, Washington 98109, USA
    Nature 437:94-100. 2005
    ..More generally, our analyses suggest an evolutionary cycle between segmental polymorphisms and genome rearrangements...
  9. ncbi Chromosome translocations in multiple myeloma
    P L Bergsagel
    Department of Medicine, Division of Hematology and Oncology, Weill Medical College of Cornell University, New York, NY, USA
    Oncogene 20:5611-22. 2001
    ..The fact that so many different primary transforming events give rise to tumors with the same phenotype suggests that there is only a single fate available for the transformed cell...
  10. pmc The neurobeachin gene is disrupted by a translocation in a patient with idiopathic autism
    D Castermans
    J Med Genet 40:352-6. 2003
  11. pmc The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations
    D O Ferguson
    Howard Hughes Medical Institute, The Children s Hospital, The Center for Blood Research, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 97:6630-3. 2000
    ..We conclude that nonhomologous DNA end-joining plays a crucial role as a caretaker of the mammalian genome, and that an alternative repair pathway exists that often leads to nonreciprocal translocations...
  12. ncbi Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer
    Scott A Tomlins
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109 0602, USA
    Science 310:644-8. 2005
    ..These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer...
  13. pmc No requirement for V(D)J recombination in p53-deficient thymic lymphoma
    M J Liao
    Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill Medical School, Chapel Hill, North Carolina 27599, USA
    Mol Cell Biol 18:3495-501. 1998
  14. ncbi Common fragile sites as targets for chromosome rearrangements
    Martin F Arlt
    Department of Human, Genetics University of Michigan, 4909 Buhl Box 0618, 1241 E Catherine Street, Ann Arbor, MI 48109, USA
    DNA Repair (Amst) 5:1126-35. 2006
    ..Here we review the relationship of fragile sites to chromosome rearrangements, particularly in tumor cells, and discuss the mechanisms that may be involved...
  15. ncbi New insights to the MLL recombinome of acute leukemias
    C Meyer
    Diagnostic Center of Acute Leukemia, Institute of Pharmaceutical Biology, ZAFES, University of Frankfurt, Frankfurt Main, Germany
    Leukemia 23:1490-9. 2009
    ..Moreover, we describe for the first time the genetic network of reciprocal MLL gene fusions deriving from complex rearrangements...
  16. ncbi BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma
    Christopher A French
    Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Cancer Res 63:304-7. 2003
    ..Very few fusion oncogenes have been identified in epithelial tumors, and BRD4-NUT is the first fusion oncogene mechanism identified in a highly lethal form of carcinoma...
  17. pmc Processive DNA synthesis observed in a polymerase crystal suggests a mechanism for the prevention of frameshift mutations
    Sean J Johnson
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 100:3895-900. 2003
  18. pmc Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma
    A J Crew
    Section of Molecular Carcinogenesis, Haddow Laboratories, Belmont, Sutton, Surrey
    EMBO J 14:2333-40. 1995
    ..Sequence analysis has demonstrated heterogeneity in the fusion transcripts with the formation of two distinct SYT-SSX1 fusion junctions and two distinct SYT-SSX2 fusion junctions...
  19. ncbi T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma
    Berthold Streubel
    Department of Pathology, Division of Oncology, Vienna General Hospital, University of Vienna, Vienna, Austria
    Blood 101:2335-9. 2003
    ..In contrast to t(11;18)(q21;q21)(+) MALT lymphomas, those with t(14;18)(q32;q21) may harbor additional genetic abnormalities...
  20. ncbi Impact of the KU80 pathway on NHEJ-induced genome rearrangements in mammalian cells
    Josee Guirouilh-Barbat
    UMR CNRS CEA 217, Laboratoire d étude des Mécanismes de la Recombinaison, Direction des Sciences du Vivant, Departement de Radiobiologie et Radiopathologie, 18 route du Panorama, 92265 Fontenay aux Roses Cedex, France
    Mol Cell 14:611-23. 2004
    ..Thus these processes should represent prominent pathways for DSB-induced genetic instability in mammalian cells...
  21. ncbi Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains
    Jacob A Aten
    Center for Microscopical Research, Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, P O Box 22700, 1100 DE Amsterdam, Netherlands
    Science 303:92-5. 2004
    ..Our results support the breakage-first theory to explain the origin of chromosomal translocations...
  22. pmc AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations
    Davide F Robbiani
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
    Cell 135:1028-38. 2008
    ..Thus, in addition to producing somatic mutations and DNA breaks in antibody genes, AID is also responsible for the DNA lesions in oncogenes that are required for their translocation...
  23. pmc Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease
    T Goossens
    Institute for Genetics, University of Cologne, 50931 Cologne, Germany
    Proc Natl Acad Sci U S A 95:2463-8. 1998
  24. ncbi IgH class switching and translocations use a robust non-classical end-joining pathway
    Catherine T Yan
    Howard Hughes Medical Institute, of Genetics, Boston, Massachusetts 02115, USA
    Nature 449:478-82. 2007
    ..In the absence of C-NHEJ, this alternative end-joining pathway also frequently joins Igh locus breaks to other chromosomes to generate translocations...
  25. pmc Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations
    Miguel R Branco
    MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom
    PLoS Biol 4:e138. 2006
    ..These findings suggest that local chromatin conformation and gene transcription influence the extent with which chromosomes interact and affect their overall properties, with direct consequences for cell-type specific genome stability...
  26. ncbi The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers
    M Ohta
    Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania, USA
    Cell 84:587-97. 1996
    ..Aberrant transcripts of the FHIT locus were found in approximately 50% of esophageal, stomach, and colon carcinomas...
  27. pmc Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157
    Qi Jin
    State Key Laboratory for Molecular Virology and Genetic Engineering, Beijing 100052, China
    Nucleic Acids Res 30:4432-41. 2002
    ..coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis...
  28. ncbi In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia
    Joseph L Wiemels
    Laboratory for Molecular Epidemiology, Department of Epidemiology and Biostatistics, University of California San Francisco 94143 0560, USA
    Blood 99:3801-5. 2002
  29. ncbi The loss of a single telomere can result in instability of multiple chromosomes in a human tumor cell line
    Laure Sabatier
    Laboratoire de Radiologie et Oncologie, Commissariat a l Energie Atomique, Fontenay aux Roses, France
    Mol Cancer Res 3:139-50. 2005
    ..Factors promoting telomere loss are therefore likely to have an important role in generating the karyotype evolution associated with human cancer...
  30. pmc Palindrome-mediated chromosomal translocations in humans
    Hiroki Kurahashi
    Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470 1192, Japan
    DNA Repair (Amst) 5:1136-45. 2006
    ..We propose that the PATRR adopts a cruciform structure in male meiotic cells, creating genomic instability that leads to the recurrent translocation...
  31. ncbi Translocations involving c-myc and c-myc function
    L M Boxer
    Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California CA 94305, USA
    Oncogene 20:5595-610. 2001
    ..Complete removal of c-myc results in slowed cell growth and proliferation, suggesting that while c-myc is not required for cell proliferation, it acts as an integrator and accelerator of cellular metabolism and proliferation...
  32. ncbi Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation
    Francesca Giannelli
    Department of Internal Medicine, University of Florence, School of Medicine, Italy
    Blood 102:1196-201. 2003
    ..This in turn suggests that antiviral treatment may help prevent or treat HCV-related LPDs...
  33. ncbi MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia
    Scott A Armstrong
    Departments of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Nat Genet 30:41-7. 2002
    ..Establishing that MLL is a unique entity is critical, as it mandates the examination of selectively expressed genes for urgently needed molecular targets...
  34. pmc Cruciform DNA structure underlies the etiology for palindrome-mediated human chromosomal translocations
    Hiroki Kurahashi
    Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470 1192, Japan
    J Biol Chem 279:35377-83. 2004
    ..Our data imply that for human chromosomes, translocation susceptibility is mediated by PATRRs and likely results from their unstable conformation...
  35. ncbi Efficient sorting of genomic permutations by translocation, inversion and block interchange
    Sophia Yancopoulos
    The Feinstein Institute for Medical Research North Shore LIJ Health System, Manhasset, NY 11030, USA
    Bioinformatics 21:3340-6. 2005
    ..We seek a universal operation underlying a more inclusive set of evolutionary operations and yielding a tractable genomic distance with simple mathematical form...
  36. ncbi AID is required for c-myc/IgH chromosome translocations in vivo
    Almudena R Ramiro
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA
    Cell 118:431-8. 2004
    ..Here we report that AID is essential for the c-myc/IgH chromosome translocations induced by IL6...
  37. ncbi Differential expression of a novel ankyrin containing E3 ubiquitin-protein ligase, Hace1, in sporadic Wilms' tumor versus normal kidney
    Michael S Anglesio
    Department of Pathology, British Columbia Research Institute for Children s and Women s Health, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada
    Hum Mol Genet 13:2061-74. 2004
    ..Our findings implicate Hace1 as a novel ubiquitin-protein ligase and demonstrate that its expression is very low in primary Wilms' tumors...
  38. ncbi Molecular diagnosis of Burkitt's lymphoma
    Sandeep S Dave
    National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    N Engl J Med 354:2431-42. 2006
    ..We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma...
  39. ncbi Molecular mechanisms underlying human synovial sarcoma development
    N R dos Santos
    Department of Human Genetics, University Hospital Nijmegen, Nijmegen, The Netherlands
    Genes Chromosomes Cancer 30:1-14. 2001
    ..Together, these studies have provided mechanistic clues about how the SYT-SSX fusion proteins may trigger synovial sarcoma development...
  40. pmc The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma
    Konstanze Pechloff
    Third Medical Department, Technical University of Munich, Klinikum rechts der Isar, 81675 Munich, Germany
    J Exp Med 207:1031-44. 2010
    ..Our work demonstrates that constitutively enforced antigen receptor signaling can, in principle, act as a powerful oncogenic driver. Moreover, we establish a robust clinically relevant and genetically tractable model of human PTCL...
  41. pmc Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma
    Brian C H Chiu
    Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 4402, USA
    Blood 108:1363-9. 2006
    ..These results suggest that defining subsets of NHL according to t(14;18) status is a useful approach for etiologic research...
  42. ncbi The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8(ETO) family
    T Gamou
    Radiobiology Division, National Cancer Center Research Institute, Tokyo, Japan
    Blood 91:4028-37. 1998
    ..Thus, the AML1-MTG16 gene fusion in t(16;21) leukemia results in the production of a protein that is very similar to the AML1-MTG8 chimeric protein...
  43. pmc Identification of AML-1 and the (8;21) translocation protein (AML-1/ETO) as sequence-specific DNA-binding proteins: the runt homology domain is required for DNA binding and protein-protein interactions
    S Meyers
    Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105
    Mol Cell Biol 13:6336-45. 1993
    ..The hybrid product, AML-1/ETO, which results from the (8;21) translocation and retains the runt homology domain, both recognizes the AML-1 consensus sequence and interacts with other cellular proteins...
  44. ncbi SHOX mutations in dyschondrosteosis (Leri-Weill syndrome)
    V Belin
    Département de Génétique et Unité de Recherches sur les Handicaps Génétiques de l Enfant INSERM U393, Hopital des Enfants Malades, Paris, France
    Nat Genet 19:67-9. 1998
    ..Here, we report large-scale deletions (in seven families) and a nonsense mutation (in one family) of SHOX in patients with DCS and show that Langer mesomelic dwarfism results from homozygous mutations at the DCS locus...
  45. pmc Nucleotide-resolution mapping of topoisomerase-mediated and apoptotic DNA strand scissions at or near an MLL translocation hotspot
    Marc Edouard Mirault
    Unit of Health and Environment, Centre de Recherche du Centre Hospitalier Universitaire de Quebec Centre Hospitalier de l Universite Laval, Quebec City, Quebec, Canada
    Am J Hum Genet 79:779-91. 2006
    ..ELMPCR provides a new tool for investigating the role of DNA topoisomerases in fundamental genetic processes and translocations associated with cancer treatments involving topoisomerase-targeted drugs...
  46. pmc Signatures of selection in fusion transcripts resulting from chromosomal translocations in human cancer
    Iñigo Ortiz de Mendíbil
    Department of Genetics, University of Navarra, Pamplona, Spain
    PLoS ONE 4:e4805. 2009
    ..However, it has also been suggested that functional constraints might contribute to delimit the position of translocation breakpoints within the genes involved, but a quantitative analysis of such contribution has been lacking...
  47. ncbi The asynaptic chromatin in spermatocytes of translocation carriers contains the histone variant gamma-H2AX and associates with the XY body
    R Sciurano
    Biologia Celular, CIR, Facultad de Medicina, Universidad de Buenos Aires, Argentina
    Hum Reprod 22:142-50. 2007
    ..Because in many of these carriers spermatogenesis is deeply disturbed at the spermatocyte level, the association of autosomal chromatin with the XY body may impair the spermatocyte life...
  48. ncbi Mouse c-myc oncogene is located on chromosome 15 and translocated to chromosome 12 in plasmacytomas
    S Crews
    Science 218:1319-21. 1982
    ..The translocated c-myc sequence is not the same oncogene detected in urine plasmacytomas by the NIH-3T3 cell transformation assay...
  49. pmc The gene SCL is expressed during early hematopoiesis and encodes a differentiation-related DNA-binding motif
    C G Begley
    Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, MD 20814
    Proc Natl Acad Sci U S A 86:10128-32. 1989
    ..SCL mRNA is observed in "early" hematopoietic tissues. Taken together, these studies lead to the speculation that SCL plays a role in differentiation and/or commitment events during hematopoiesis...
  50. pmc Chromosomal rearrangement interferes with meiotic X chromosome inactivation
    David Homolka
    Institute of Molecular Genetics, Academy of Sciences of Czech Republic, 142 20 Prague 4, Czech Republic
    Genome Res 17:1431-7. 2007
    ..Our findings provide direct evidence on the MSUC acting at the mRNA level, and implicate that autosomal asynapsis in meiosis may cause male sterility by interfering with meiotic sex chromosome inactivation...
  51. ncbi Recurrent chromosome aberrations in cancer
    F Mitelman
    Department of Clinical Genetics, University Hospital, SE 221 85, Lund, Sweden
    Mutat Res 462:247-53. 2000
    ..Data obtained during recent years strongly suggest that corresponding breakthroughs will be achieved in solid tumors within a not-too-distant future...
  52. ncbi A novel gene, Translin, encodes a recombination hotspot binding protein associated with chromosomal translocations
    K Aoki
    Department of Immunology, National Institute of Health, Tokyo, Japan
    Nat Genet 10:167-74. 1995
  53. pmc MLL fusions: pathways to leukemia
    Han Liu
    Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Cancer Biol Ther 8:1204-11. 2009
    ..Here, we summarize the critical biological and pathological activities of MLL and MLL fusions, and discuss available models and potential therapeutic targets of MLL associated leukemias...
  54. ncbi Origins of chromosome translocations in childhood leukaemia
    Mel F Greaves
    LRF Centre for Cell and Molecular Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Nat Rev Cancer 3:639-49. 2003
    ..How, when and where do translocations arise? And can these insights aid our understanding of the natural history, pathogenesis and causes of leukaemia?..
  55. ncbi A novel sequence-based approach to localize translocation breakpoints identifies the molecular basis of a t(4;22)
    Manjunath A Nimmakayalu
    Division of Human Genetics and Molecular Biology, The Children s Hospital of Philadelphia, PA 19104, USA
    Hum Mol Genet 12:2817-25. 2003
    ..The sequence of this breakpoint further suggests that a stem-loop secondary structure mechanism is responsible for the formation of other, non-recurrent translocations involving LCR-B of 22q11.2...
  56. pmc AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations
    Y Yuan
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 98:10398-403. 2001
    ..The hMRP8-AML1-ETO-transgenic mice provide an excellent model that can be used to isolate additional genetic events and to further understand the molecular pathogenesis of AML1-ETO-related leukemia...
  57. ncbi Germ line insertion of mtDNA at the breakpoint junction of a reciprocal constitutional translocation
    J E Willett-Brozick
    Department of Psychiatry, The University of Pittsburgh School of Medicine, 3811 O'Hara Street R1445, Pittsburgh, PA 15213, USA
    Hum Genet 109:216-23. 2001
    ..Our findings also provide evidence for a previously unrecognized insertional mechanism in human, by which non-mobile extra-chromosomal fragments can be inserted into the genome at DSB repair junctions...
  58. ncbi Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt
    P Erickson
    Division of Medical Oncology, University of Colorado Health Sciences and Cancer Center, Denver 80262
    Blood 80:1825-31. 1992
    ..The critical consequence of the translocation is the juxtaposition of 5' sequences of AML1 to 3' sequences of ETO, oriented telomere to centromere on the der(8) chromosome...
  59. pmc Myc dynamically and preferentially relocates to a transcription factory occupied by Igh
    Cameron S Osborne
    Laboratory of Chromatin and Gene Expression, The Babraham Institute, Cambridge, United Kingdom
    PLoS Biol 5:e192. 2007
    ..Furthermore, the data imply a direct link between the nonrandom interchromosomal organization of transcribed genes at transcription factories and the incidence of specific chromosomal translocations...
  60. ncbi The protooncogene TCL1 is an Akt kinase coactivator
    J Laine
    Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell 6:395-407. 2000
    ..In vivo, TCL1 forms trimers, which associate with Akt. TCL1 facilitates the oligomerization and activation of Akt. Our data show that TCL1 is a novel Akt kinase coactivator, which promotes Akt-induced cell survival and proliferation...
  61. ncbi A Novel TRAF6 binding site in MALT1 defines distinct mechanisms of NF-kappaB activation by API2middle dotMALT1 fusions
    Heidi Noels
    Human Genome Laboratory, Department for Molecular and Developmental Genetics, Flanders Institute for Biotechnology VIB, B 3000 Leuven, Belgium
    J Biol Chem 282:10180-9. 2007
    ..Taken together, these data reveal distinct mechanisms of NF-kappaB activation by the different API2.MALT1 fusion variants with an essential role for TRAF6...
  62. pmc IL-6 transgenic mouse model for extraosseous plasmacytoma
    Alexander L Kovalchuk
    Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 99:1509-14. 2002
    ..These findings provide a unique model of extramedullary PCT for studies on pathogenesis and treatment and suggest a previously unappreciated role for IL-6 in the genesis of germinal center-derived lymphomas...
  63. ncbi siRNA-mediated AML1/MTG8 depletion affects differentiation and proliferation-associated gene expression in t(8;21)-positive cell lines and primary AML blasts
    J Dunne
    Cancer Research UK Medical Oncology Laboratory, Barts and the London School of Medicine, London, UK
    Oncogene 25:6067-78. 2006
    ..Furthermore, the results suggest that the specific targeting of AML1/MTG8 function may be a promising approach for complementing existing treatment strategies...
  64. ncbi Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry
    Brunangelo Falini
    Institute of Hematology, University of Perugia, Italy
    Blood 99:409-26. 2002
  65. ncbi A chromosomal translocation in cyclin D1-negative/cyclin D2-positive mantle cell lymphoma fuses the CCND2 gene to the IGK locus
    Stefan Gesk
    Blood 108:1109-10. 2006
  66. ncbi An Atlas on genes and chromosomes in oncology and haematology
    J L Huret
    Genetics, Dept of Medical Information, UMR 8125 CNRS IGR, University Hospital, F 86021 Poitiers, France
    Cell Mol Biol (Noisy-le-grand) 50:805-7. 2004
    ..It contributes to 'meta-medicine', a mediation using new information technology, between the overflowing information provided by the scientific community and the individual practitioner...
  67. ncbi Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia
    T Nakamura
    Mammalian Genetics Laboratory, NCI Frederick Cancer Research and Development Center, Maryland 21702, USA
    Nat Genet 12:154-8. 1996
  68. ncbi Lymphoid malignancies: the dark side of B-cell differentiation
    A L Shaffer
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Immunol 2:920-32. 2002
    ..The similarities and differences between malignant and normal B cells indicate strategies for the treatment of these cancers...
  69. pmc Follicular lymphoma-like B cells in healthy individuals: a novel intermediate step in early lymphomagenesis
    Sandrine Roulland
    Centre d immunologie de Marseille Luminy, Universite de la Mediterranee, 13288 Marseille, France
    J Exp Med 203:2425-31. 2006
    ..These findings strongly impact both on the current understanding of disease progression and on the proper handling of t(14;18) frequency in blood as a potential early biomarker for lymphoma...
  70. pmc Positional stability of single double-strand breaks in mammalian cells
    Evi Soutoglou
    National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Nat Cell Biol 9:675-82. 2007
    ..These results support a contact-first model in which chromosome translocations predominantly form among spatially proximal DSBs...
  71. ncbi Identification of genes associated with chemotherapy crossresistance and treatment response in childhood acute lymphoblastic leukemia
    Sanne Lugthart
    Hematological Malignancy Program, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Cell 7:375-86. 2005
    ..The expression of these genes discriminated treatment outcome in two independent patient populations, identifying a subset of patients with a markedly inferior outcome (37% +/- 13% 5 year DFS)...
  72. ncbi BCL2 accelerates inflammation-induced BALB/c plasmacytomas and promotes novel tumors with coexisting T(12;15) and T(6;15) translocations
    Santiago Silva
    Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden
    Cancer Res 63:8656-63. 2003
    ..Accelerated plasmacytomagenesis in strain C.BCL2 may be useful for designing and testing BCL2 inhibition strategies in human plasma cell tumors overexpressing BCL2, such as Waldenström's macroglobulinemia and multiple myeloma...
  73. ncbi Translocation t(14;18) and gain of chromosome 18/BCL2: effects on BCL2 expression and apoptosis in B-cell non-Hodgkin's lymphomas
    E Galteland
    Department of Radiation Biology, The Norwegian Radium Hospital, Oslo, Norway
    Leukemia 19:2313-23. 2005
    ..33 that did not include the BCL2 gene. The 11 cases with 18q gain only showed a consensus region encompassing 18q21.2-18q21.32 and 18q21.33, which contain PMAIP1/MALT1 and BCL2, respectively...
  74. ncbi Mechanisms of B-cell lymphoma pathogenesis
    Ralf Kuppers
    Institute for Cell Biology Tumor Research, University of Duisburg Essen, Medical School, Germany
    Nat Rev Cancer 5:251-62. 2005
    ..Recent insights into the lymphomagenic role of factors supplied by the microenvironment also offer new therapeutic strategies...
  75. ncbi A signaling pathway mediating downregulation of BCL6 in germinal center B cells is blocked by BCL6 gene alterations in B cell lymphoma
    Masumichi Saito
    Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA
    Cancer Cell 12:280-92. 2007
    ..A subset of DLBCL displays chromosomal translocations or mutations that disrupt the IRF4-responsive region in the BCL6 promoter and block its downregulation by CD40 signaling...
  76. pmc Negative autoregulation of BCL-6 is bypassed by genetic alterations in diffuse large B cell lymphomas
    Xing Wang
    Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 99:15018-23. 2002
    ..Our results not only demonstrate an important mechanism governing the expression of BCL-6, but also explain how BCL-6 is deregulated in a large number of DLBCL patients, providing a better understanding of BCL-6-related lymphomagenesis...
  77. ncbi Chromosome translocations: dangerous liaisons revisited
    J D Rowley
    Department of Medicine, University of Chicago Medical Center, Illinois 60637, USA
    Nat Rev Cancer 1:245-50. 2001
    ..The prevailing view for most of this period was that chromosome changes were secondary events. What happened to change this view?..
  78. pmc Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice
    S Suematsu
    Division of Immunology, Osaka University, Japan
    Proc Natl Acad Sci U S A 89:232-5. 1992
    ..These results provide firm evidence of the critical role of IL-6 in the plasmacytoma development...
  79. ncbi The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25
    D Y Nishimura
    Department of Pediatrics, University of Iowa, Iowa City 52242, USA
    Nat Genet 19:140-7. 1998
    ..Furthermore, FKHL7 was found to harbour mutations in patients diagnosed with Rieger anomaly (RA), Axenfeld anomaly (AA) and iris hypoplasia (IH). This study demonstrates that mutations in FKHL7 cause a spectrum of glaucoma phenotypes...
  80. pmc Cycles of chromosome instability are associated with a fragile site and are increased by defects in DNA replication and checkpoint controls in yeast
    Anthony Admire
    Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA
    Genes Dev 20:159-73. 2006
    ..Cycles of instability of this normal yeast chromosome may be relevant to chromosome instability of mammalian fragile sites and of chromosomes in cancer cells...
  81. ncbi MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma
    Dolors Sanchez-Izquierdo
    Department of Hematology and Medical Oncology, Hospital Clinico, University of Valencia, Spain
    Blood 101:4539-46. 2003
    ..Together, these data implicate MALT1 as a dominant oncogene that may play a role in the pathogenesis of B-NHL...
  82. pmc Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML1-ETO translocation
    Cristina G de Guzman
    Department of Human Genetics, University of Alabama at Birmingham, 1824 6th Avenue South, Birmingham, AL 35294, USA
    Mol Cell Biol 22:5506-17. 2002
    ..This suggests that the principal contribution of AML1-ETO to acute myeloid leukemia is the inhibition of multiple developmental pathways...
  83. ncbi Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development
    Y Gao
    Howard Hughes Medical Institute, The Children s Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 404:897-900. 2000
    ..Our findings support a crucial role for the non-homologous end-joining pathway as a caretaker of the mammalian genome, a role required both for normal development and for suppression of tumours...
  84. ncbi Mechanisms of chromosomal translocations in B cell lymphomas
    R Kuppers
    Institute of Cancer Genetics, Columbia University, New York, NY 10032, USA
    Oncogene 20:5580-94. 2001
  85. ncbi Template switching during break-induced replication
    Catherine E Smith
    Department of Microbiology, Columbia University Medical Center, 701 West 168th Street, New York, New York 10032, USA
    Nature 447:102-5. 2007
    ..This dynamic process could function to promote gene conversion by capture of the displaced invading strand at two-ended DSBs to prevent BIR...
  86. ncbi Incidence of additional genetic changes in the TEL and AML1 genes in DCOG and COALL-treated t(12;21)-positive pediatric ALL, and their relation with drug sensitivity and clinical outcome
    W A G Stams
    Erasmus MC, Sophia Children s Hospital, Erasmus University Medical Center Rotterdam, Division of Pediatric Oncology Hematology, Rotterdam, The Netherlands
    Leukemia 20:410-6. 2006
    ..78, 95% CI 1.45-23.0; P=0.01) is an independent prognostic factor in DCOG- and COALL-treated t(12;21)-positive ALL...
  87. ncbi Role of AML1/Runx1 in the pathogenesis of hematological malignancies
    Mineo Kurokawa
    Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Bunkyo ku, Tokyo113 8655, Japan
    Cancer Sci 94:841-6. 2003
    ..However, AML1-related translocations or haploinsufficiency of AML1 are not immediately leukemogenic in animal models, suggesting that additional genetic events are required for the development of full-blown leukemia...
  88. ncbi A mutational analysis of Caenorhabditis elegans in space
    Yang Zhao
    Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364 2350 Health Sciences Mall, Vancouver, BC, Canada
    Mutat Res 601:19-29. 2006
  89. pmc AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations
    Davide F Robbiani
    The Rockefeller University, New York, NY 10065, USA
    Mol Cell 36:631-41. 2009
    ..We conclude that AID produces DSBs throughout the genome, which can lead to lymphoma-associated chromosome translocations in mature B cells...
  90. ncbi The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas
    J Dierlamm
    Department of Oncology and Hematology, University Hospital Eppendorf, Hamburg, Germany
    Blood 93:3601-9. 1999
    ..As a result, the reciprocal transcript was not present, strongly suggesting that the API2-MLT fusion is involved in the oncogenesis of MALT lymphoma...
  91. ncbi Core-binding factors in haematopoiesis and leukaemia
    Nancy A Speck
    Department of Biochemisty, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Nat Rev Cancer 2:502-13. 2002
  92. pmc Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites
    Allison A Burrow
    Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157 1016, USA
    BMC Genomics 10:59. 2009
    ..However, there has been no comprehensive and quantitative examination of the location of fragile sites in relation to all chromosomal aberrations...
  93. ncbi Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22
    J Groffen
    Cell 36:93-9. 1984
    ..The highly specific presence of a chromosomal breakpoint within bcr in Ph'-positive CML patients strongly suggests the involvement of bcr in this type of leukemia...
  94. ncbi The topological organization of chromosomes 9 and 22 in cell nuclei has a determinative role in the induction of t(9,22) translocations and in the pathogenesis of t(9,22) leukemias
    S Kozubek
    Institute of Biophysics, Academy of Sciences, Brno, Czech Republic
    Chromosoma 108:426-35. 1999
    ..HL60 cells and bone marrow cells. This finding suggests that the specific chromatin structure mentioned might be responsible for the high rate of induction of t(9;22)-positive leukemias in the human population...
  95. ncbi Translocation, breakage and truncated transcripts of c-myc oncogene in murine plasmacytomas
    L W Stanton
    Nature 303:401-6. 1983
    ..The second and third exons of the mouse c-myc gene are substantially conserved in the v-myc gene of the avian retrovirus, MC29...
  96. ncbi The Ashbya gossypii genome as a tool for mapping the ancient Saccharomyces cerevisiae genome
    Fred S Dietrich
    Biozentrum der Universitat Basel, Klingelbergstrasse 50, CH 4056 Basel, Switzerland
    Science 304:304-7. 2004
    ..cerevisiae included a whole genome duplication or fusion of two related species and showed, through inferred ancient gene orders, which of the duplicated genes lost one copy and which retained both copies...
  97. ncbi Novel genomic imbalances and chromosome translocations involving c-myc gene in Burkitt's lymphoma
    D B Zimonjic
    Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA
    Leukemia 15:1582-8. 2001
    ..Duplication of the bands 1q23-24 commonly observed in EBV-negative lines was identified only in highly tumorigenic CA46 cells suggesting that this region harbor gene(s) associated with tumor cell invasiveness...
  98. pmc Spatial genome organization in the formation of chromosomal translocations
    Karen J Meaburn
    National Cancer Institute, NIH, Bethesda, MD 20892, United States
    Semin Cancer Biol 17:80-90. 2007
    ..We review here the emerging principles of spatial genome organization and discuss the implications of non-random spatial genome organization for the genesis and specificity of cancerous chromosomal translocations...
  99. pmc Involvement of the TCL5 gene on human chromosome 1 in T-cell leukemia and melanoma
    L R Finger
    Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140
    Proc Natl Acad Sci U S A 86:5039-43. 1989
    ..Rearrangement of the TCL5 locus in a human melanoma cell line carrying a del(1p32) further implies that the TCL5 gene may play a role in malignant transformation...
  100. pmc Synovial sarcoma: from genetics to genetic-based animal modeling
    Malay Haldar
    Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112 5331, USA
    Clin Orthop Relat Res 466:2156-67. 2008
  101. pmc Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell-like diffuse large B cell lymphoma
    Georg Lenz
    Metabolism Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute NCI, National Institutes of Health NIH, Bethesda, MD 20892, USA
    J Exp Med 204:633-43. 2007
    ..Accordingly, aberrant switch recombination was responsible for translocations in ABC DLBCLs involving BCL6, MYC, and a novel translocation partner, SPIB...

Research Grants70

  1. Chromatin structure maintenance and cancer
    Jianxin You; Fiscal Year: 2013
    ..Brd4 is also a target of the oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV), and the genetic translocation t(15;19) that defines a highly lethal carcinoma...
  2. Risk Factors for Molecularly Defined Subgroups of Lymphoma: A Pooled Analysis
    Brian Chiu; Fiscal Year: 2008
    ..This project directly responds to the NCI strategic plan for cancer preemption because it can elucidate the etiology of NHL. [unreadable] [unreadable] [unreadable]..
    Michael Fasullo; Fiscal Year: 2004
    ..abstract_text> ..
  4. Activating liver carcinogens in yeast by expressing CYP450 polymorphisms
    Michael Fasullo; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  5. Full karyotype single cell interphase analysis
    Santiago Munne; Fiscal Year: 2005
    ..In phase-I we propose to develop two of the three sets of probes, and to test that these probes will work with 90% efficiency after three rounds of hybridization in single polar bodies. ..
    Michael Lieber; Fiscal Year: 2004
    ..Corresponding studies of such regions on minichromosomes will permit the testing of the effects of the direction of DNA replication and transcription. ..
    James Haber; Fiscal Year: 2006
    ..abstract_text> ..
  8. Prognostic Models in Diffuse Large B-Cell Lymphoma
    Izidore S Lossos; Fiscal Year: 2010
    ..Further, establishment of a paraffin-based RNA prognostic model using the new methodology of RNA extraction could serve as a paradigm for other lymphomas and tumors. ..
  9. AML1 in Hematopoietic Cell Development
    ROBERT LORSBACH; Fiscal Year: 2006
    ..abstract_text> ..
  10. Hedgehog signaling as a novel regulator of hematopoiesis
    Iannis Aifantis; Fiscal Year: 2007
    ..We will complement these experiments with the study of novel Hh activating mouse mutants in which we will define the exact role of the Gli factors in the regulation of mammalian lymphopoiesis and hematopoiesis. ..
  11. Ditag technologies for complete transcriptome annotation
    Yijun Ruan; Fiscal Year: 2006
    ..We seek to identify all genes that are responsive to p53, and to ascertain through GIS-ChIP cloning and through our novel GIS analysis strategy all possible cis-regulatory fragments. [unreadable] [unreadable]..
  12. Mechanistic Effects of Organic Selenium Against Colon C
    Mark Nelson; Fiscal Year: 2006
    ..abstract_text> ..
  13. Pharmacologic modulation of chromatin remodeling in leu*
    Guido Marcucci; Fiscal Year: 2006
    ..Further, we believe that this schedule is amenable to future combination-based approaches. [unreadable] [unreadable]..
  14. Identification of Pericentromeric Imbalances
    Lisa Shaffer; Fiscal Year: 2005
    ..The identification of deletions or duplications in the pericentromeric regions may delineate new syndromes or uncover the etiology of established syndromes. ..
  15. Targeting Akt/NF-kappa beta for Pancreatic Cancer Therapy
    Fazlul Sarkar; Fiscal Year: 2007
    ..These results will provide mechanistic as well as pre-clinical data in support of our hypotheses and may open new and novel avenues for the treatment of human pancreatic cancer. ..
  16. Population genetics of transgenes in mosquito vectors
    Fred Gould; Fiscal Year: 2008
    ..A user-friendly form of the models as well as an accessible manual will be developed and placed on the internet. ..
  17. Genomic & Genetic Characterization of Amplicons in GBMs
    Lynda Chin; Fiscal Year: 2007
    ..The highest potential candidate glioma oncogene will be further validated by rigorous in vivo transgenesis study. ..
    Matthew State; Fiscal Year: 2006
    ..abstract_text> ..
  19. T(15;19) in Aggressive Pediatric Carcinoma
    Christopher French; Fiscal Year: 2006
    ..These studies will also reveal the range of primary sites from which t(15;19)+ carcinomas arise. ..
  20. Characterization of the 11q13 Amplicon in Oral Cancer
    Susanne Gollin; Fiscal Year: 2006
    ..The results of this study may lead to targeted methods for prevention, early detection, therapy, and/or eradication of cells harboring gene amplification. ..
    Terry Ashley; Fiscal Year: 2004
    ..Our results will lead to a better understanding of some of the underlying causes of male sterility and could also lead to new insights into development of a male contraceptive. ..
  22. Regulation of Nanog in DNA damage response, development and tumorigenesis
    Yang Xu; Fiscal Year: 2010
    ..In addition, these studies will shed light on mechanism that maintains genetic stability in human ESCs, which have a great potential for future human cell/tissue replacement therapy. ..
  23. Molecular Analysis of Del(9q) Acute Myeloid Leukemia
    David A Sweetser; Fiscal Year: 2010
    ..The information from this study will hopefully aid in the rational design of effective targeted therapies and may have relevance to the pathogenesis of other cancers. ..
    CAROLYN FELIX; Fiscal Year: 2004
    ..Risk factors for treatment-related leukemia are poorly understood. Predictive biomarker assays will enable rational modifications of primary cancer therapies and provide new opportunities for early intervention. ..
    PAMELA CORRELL; Fiscal Year: 2002
    ..By understanding, in more detail, the regulation of macrophage activation, the PI hopes to begin to identify targets for suppression of the tissue-damaging effects of inflammation without compromising the host immune response. ..
    BARRY FINETTE; Fiscal Year: 2002
    ..Results obtained from these studies will provide fundamental insights regarding the clinical relevance of age-specific, spontaneous and environmentally induced somatic mutations in children. ..
    Thoru Pederson; Fiscal Year: 2001
    ..The same studies should provide information on sequences required for nuclear export. These two inter-related projects test the hypothesis that the nucleolus is a more pluri-functional organelle than previously thought. ..
    David Maloney; Fiscal Year: 2002
    ..III. Determine the role of the mAb FC region in mediating anti- proliferative effects of anti-CD20 mAbs in xenografts of B cell NHL lines in NOD/SCID mice. ..
    Lynda Chin; Fiscal Year: 2002
    CAROLYN FELIX; Fiscal Year: 2007
    ..Solving the mechanism of leukemogenesis of the DNA topoisomerase II inhibitors is highly relevant to the targeted prevention of this usually fatal complication of anticancer treatment. ..
  31. Activation of BCL-2 in Hematologic Malgnancies
    LINDA BOXER; Fiscal Year: 2007
    ..These studies will provide new information that can be used to treat the disease in humans. ..
  32. The Role of SLITRK1 in Tourette and Related Disorders
    Matthew W State; Fiscal Year: 2010
    ..The purpose of this study is to better understand .what causes TD by identifying additional abnormalities in the SLITRK1 gene and by investigating the impact of these unusual genetic changes on the developing brain. ..
  33. Cytokine Regulated Growth Of Hematopoietic Cells
    James Ihle; Fiscal Year: 2007
    ..Both genetic approaches and biochemical approaches are proposed to identify components of this pathway. ..
  34. Loss of FLJ13639 Expression in Acute Leukemia
    Keshav K Singh; Fiscal Year: 2010
    ..Confirmation of the role of the loss of FLJ13639 in leukemia prognosis, increase of chemo resistance should lead us and others, to develop new prognostic tools as well as novel, innovative therapeutic strategies. ..
  35. Phase 3 stem cell transplant for light chain amyloidosis
    Morie A Gertz; Fiscal Year: 2011
    ..In addition, the analysis of clonal precursor B cells in the periphery and kinetics of amyloid formation of the monoclonal light chain will allow us to define and determine the mechanisms of disease progression and response to therapy. ..
  36. Role of MN1-TEL and MN1 in Leukemogenesis
    Gerard C Grosveld; Fiscal Year: 2010
    ..These studies should also provide leads for the development of novel therapies for AML involving these transcription factors. ..
  37. Functional characterization of FSHR alternatively spliced variants
    Maria Lalioti; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  38. Meningioma: Risk Factors and Quality of Life
    JOSEPH LEO WIEMELS; Fiscal Year: 2010
    ..This study represents the first concentrated effort to examine environmental and genetic risk factors for meningioma. ..
  39. The role of AID protein in the host response to viral infection
    F Papavasiliou; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  40. Genetic Determinants of Host Susceptibility to Pulmonary Anthrax
    Jagjit Yadav; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  41. Role of Wnt signaling in Cervical Cancer Pathogenesis
    Aykut Uren; Fiscal Year: 2010
    ..Aykut The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page 1 Description, ..
  42. RUNX-fusion Target Genes in Normal and Leukemic Hematopoiesis
    JAMES MULLOY; Fiscal Year: 2007
    ..Understanding the modulation of the self-renewal process by these fusion proteins could give insight into the normal mechanisms of self-renewal employed by the stem cell. [unreadable] [unreadable]..
  43. Arsenic Trioxide Down-Regulates STAT3 Activity in AML
    Meir Wetzler; Fiscal Year: 2004
    ..In addition, we will attempt to identify the mode by which ATO controls the activity of STAT3 and how this effect alters the gene profile patterns and induces apoptosis. ..
  44. 2003 Genetic Toxicology Gordon Conference
    Penny Jeggo; Fiscal Year: 2003
    ..We particularly air to obtain funding to support applications from minority groupings and younger scientists. We have already identified a significant participation of women amongst our list of speakers. ..
    Mark Schlissel; Fiscal Year: 2004
  46. Angiogenesis and thalidomide therapy in multiple myeloma
    S Rajkumar; Fiscal Year: 2004
    ..This study offers a unique opportunity to serially study tumor cells and the tumor microenvironment following potential anti-angiogenic therapy. ..
    John Byrd; Fiscal Year: 2003
    ..The clinical and laboratory results of this trial will provide pharmacokinetic and pharmacodynamic information for additional correlative efforts in both single agent phase II and combination phase I studies. ..
  48. Quantitative RT-PCR: Prediction Lymphoma Transformation
    Kojo Elenitoba Johnson; Fiscal Year: 2005
  49. A PHASE 1 Study of HuD10 IN CLL/SLL PATIENTS
    John Byrd; Fiscal Year: 2002
    ..These laboratory studies combined with clinical data derived from this trial will form the basis for future phase II development of this agent in CLL/SLL. ..
  50. Molecular Stratification of Brain Tumors
    John Cowell; Fiscal Year: 2005
    ..Ultimately we will be able to develop a custom array which will allow an unbiased analysis of brain tumors in an attempt to predict clinical phenotypes such as response to therapy and prognosis. ..
    Jagjit Yadav; Fiscal Year: 2003
    ..chrysosporium constructed for this purpose, and/or in vitro assays using expressed enzymes. Optimized P450 conditions and strains will be tested in bench top models of bioremediation. ..
    Martyn Smith; Fiscal Year: 2007
    ..The overall goal is to develop new biomarkers of exposure and early effect for benzene and provide new insights into the mechanisms of benzene toxicity. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
    Bogdan Czerniak; Fiscal Year: 2006
  54. Control of Mammalian Meiotic Recombination
    Terry Ashley; Fiscal Year: 2007
    ..In addition, we will examine the effects of mutations in genes likely to be involved in control of frequency and distribution of recombination. ..
  55. Canine Brain Tumors - A New Model for Gene Discovery
    Matthew Breen; Fiscal Year: 2006
    ..Characterization of these genetic loci will help to improve the definition of molecular risk and prognosis of human and canine brain tumors, with a potentially major impact on human health. ..
    Michael Cornforth; Fiscal Year: 2002
  57. Epigenetic Targeted Therapy for Chronic Lymphocytic Leu*
    John Byrd; Fiscal Year: 2005
    ..abstract_text> ..
  58. The Role of MLL-AF9 in Acute Myeloid Leukemia
    James C Mulloy; Fiscal Year: 2010
    ..RELEVANCE (See instructions): We have recently shown that human blood stem cells can be induced to make leukemia upon introduction ..
    Heinz Ulrich Weier; Fiscal Year: 2002
    ..We will prepare stable cell lines carrying the oncogenic rearrangements for further characterization and distribution. Finally, we will examine the levels and localization of mRNAs with Northern and in situ hybridization analysis. ..
  60. The Genetics of Specific Language Impairment
    JAMES TOMBLIN; Fiscal Year: 2009
    ..The phenotypes and endophenotypes from these individuals will then be used in conjunction with the existing genotyping for additional genome-wide screens and further follow-up fine mapping studies. ..
  61. The Role of CBFb-MYH11 in Acute Myeloid Leukemia
    James C Mulloy; Fiscal Year: 2010
    ..To identify specific signals that will cooperate in the transformation to acute leukemia, defined eenetic elements and saturatine retroviral mutaeenesis will be used. ..
  62. Aneuploid Cells in the Human Placenta
    Heinz Ulrich Weier; Fiscal Year: 2006
    ..We will also have detailed information about the frequency, localization and types of aneuploid cells at the fetal-maternal interface and the effects of aneuploidy on CTB proliferation and HLA-G gene expression. ..
  63. BAC-FISH Assays for Sensitive Karyotyping of Cancer Cells
    Heinz Ulrich Weier; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  64. Collaboration on Specific Language Impairment
    JAMES TOMBLIN; Fiscal Year: 2005
    ..abstract_text> ..
  65. New Models of Human Cancer
    William Hahn; Fiscal Year: 2005
    ..Robert Weinberg and the unique resources of the Whitehead Institute to develop these new systems and to broaden my research experiences as I make the crucial transition to an independent investigator. ..
  66. Mechanisms of Nonhomologous Repair of Damaged DNA
    Sang Eun Lee; Fiscal Year: 2005
    ..Furthermore, since DSB repair by NHEJ is remarkably conserved from yeast to humans, these studies will help to dissect the similar pathways in humans. ..
  67. Markers for the Early Detection of Ovarian Cancer
    MICHAEL TAINSKY; Fiscal Year: 2007
    ..The principle is that we clone epitopes reacting with IgG in patients sera and use them to detect antibodies in sera to discriminate cancer and healthy subjects and whether we can detect disease prior to standard diagnosis. ..
    MICHAEL TAINSKY; Fiscal Year: 2002
    ..abstract_text> ..