dna mutational analysis


Summary: Biochemical identification of mutational changes in a nucleotide sequence.

Top Publications

  1. ncbi Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
    Thomas J Lynch
    Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston 02129, USA
    N Engl J Med 350:2129-39. 2004
  2. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
  3. pmc Patterns of somatic mutation in human cancer genomes
    Christopher Greenman
    Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
    Nature 446:153-8. 2007
  4. pmc A comprehensive catalogue of somatic mutations from a human cancer genome
    Erin D Pleasance
    Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 463:191-6. 2010
  5. pmc Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain
    William Pao
    Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    PLoS Med 2:e73. 2005
  6. pmc Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
    Xose S Puente
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nature 475:101-5. 2011
  7. ncbi Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database
    Audrey Petitjean
    Group of Molecular Carcinogenesis and Biomarkers, International Agency for Research on Cancer IARC, World Health Organization, Lyon, France
    Hum Mutat 28:622-9. 2007
  8. pmc A small-cell lung cancer genome with complex signatures of tobacco exposure
    Erin D Pleasance
    Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 463:184-90. 2010
  9. pmc DNMT3A mutations in acute myeloid leukemia
    Timothy J Ley
    Department of Genetics, Genome Center, Washington University, St Louis, MO 63110, USA
    N Engl J Med 363:2424-33. 2010
  10. ncbi K-ras mutations and benefit from cetuximab in advanced colorectal cancer
    Christos S Karapetis
    Flinders Medical Centre and Flinders University, Adelaide, Australia
    N Engl J Med 359:1757-65. 2008

Detail Information

Publications319 found, 100 shown here

  1. ncbi Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
    Thomas J Lynch
    Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston 02129, USA
    N Engl J Med 350:2129-39. 2004
    ..However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown...
  2. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
    ..As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma...
  3. pmc Patterns of somatic mutation in human cancer genomes
    Christopher Greenman
    Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
    Nature 446:153-8. 2007
    ..Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated...
  4. pmc A comprehensive catalogue of somatic mutations from a human cancer genome
    Erin D Pleasance
    Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 463:191-6. 2010
    ..The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic...
  5. pmc Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain
    William Pao
    Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    PLoS Med 2:e73. 2005
    ..Despite initial responses, patients eventually progress by unknown mechanisms of "acquired" resistance...
  6. pmc Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
    Xose S Puente
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nature 475:101-5. 2011
    ..It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer...
  7. ncbi Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database
    Audrey Petitjean
    Group of Molecular Carcinogenesis and Biomarkers, International Agency for Research on Cancer IARC, World Health Organization, Lyon, France
    Hum Mutat 28:622-9. 2007
    ..These results provide new insights into the factors that shape mutation patterns and influence mutation phenotype, which may have clinical interest...
  8. pmc A small-cell lung cancer genome with complex signatures of tobacco exposure
    Erin D Pleasance
    Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 463:184-90. 2010
    ..These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer...
  9. pmc DNMT3A mutations in acute myeloid leukemia
    Timothy J Ley
    Department of Genetics, Genome Center, Washington University, St Louis, MO 63110, USA
    N Engl J Med 363:2424-33. 2010
    ..The genetic alterations responsible for an adverse outcome in most patients with acute myeloid leukemia (AML) are unknown...
  10. ncbi K-ras mutations and benefit from cetuximab in advanced colorectal cancer
    Christos S Karapetis
    Flinders Medical Centre and Flinders University, Adelaide, Australia
    N Engl J Med 359:1757-65. 2008
    ..The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value...
  11. pmc Intra- and inter-tumor heterogeneity of BRAF(V600E))mutations in primary and metastatic melanoma
    Molly Yancovitz
    Department of Dermatology, New York University Langone Medical Center, New York, New York, United States of America
    PLoS ONE 7:e29336. 2012
  12. ncbi The mutation spectrum revealed by paired genome sequences from a lung cancer patient
    William Lee
    Department of Bioinformatics and Computational Biology, Genentech Inc, South San Francisco, California 94080, USA
    Nature 465:473-7. 2010
    ..We present a comprehensive view of somatic alterations in a single lung tumour, and provide the first evidence, to our knowledge, of distinct selective pressures present within the tumour environment...
  13. pmc Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin
    Ryan D Morin
    Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada
    Nat Genet 42:181-5. 2010
    ..7% of GCB DLBCLs and 7.2% of FLs and are absent from ABC DLBCLs. Our data are consistent with the notion that EZH2 proteins with mutant Tyr641 have reduced enzymatic activity in vitro...
  14. pmc Characterization of mutation spectra with ultra-deep pyrosequencing: application to HIV-1 drug resistance
    Chunlin Wang
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
    Genome Res 17:1195-201. 2007
    ..With appropriate analysis, ultra-deep pyrosequencing is a promising method for characterizing genetic diversity and detecting minor yet clinically relevant variants in biological samples with complex genetic populations...
  15. pmc Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral
    S V Tavtigian
    International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon, France
    J Med Genet 43:295-305. 2006
    ..However, clinical testing methods with high sensitivity for deleterious mutations in these genes also detect many unclassified variants, primarily missense substitutions...
  16. ncbi Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab
    Wendy De Roock
    Center for Human Genetics, University of Leuven, Leuven, Belgium
    JAMA 304:1812-20. 2010
    ..Patients with metastatic colorectal cancer who have KRAS codon 12- or KRAS codon 13-mutated tumors are presently excluded from treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab...
  17. pmc Detection of mutations in EGFR in circulating lung-cancer cells
    Shyamala Maheswaran
    Massachusetts General Hospital Cancer Center, Boston 02129, USA
    N Engl J Med 359:366-77. 2008
    ..Molecular characterization of circulating tumor cells may provide a strategy for noninvasive serial monitoring of tumor genotypes during treatment...
  18. pmc Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS)
    C R Newton
    ICI Diagnostics, Northwich, Cheshire, UK
    Nucleic Acids Res 17:2503-16. 1989
    ..Our findings are in complete agreement with allele assignments derived by direct sequencing of PCR products...
  19. ncbi Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma
    Georgina V Long
    Melanoma Institute Australia, 40 Rocklands Rd, North Sydney, New South Wales, 2060, Australia
    J Clin Oncol 29:1239-46. 2011
    ..To assess the frequency and type of oncogenic BRAF mutations in metastatic melanoma and correlate BRAF status with clinicopathologic features and outcome...
  20. ncbi Multisite analytic performance studies of a real-time polymerase chain reaction assay for the detection of BRAF V600E mutations in formalin-fixed, paraffin-embedded tissue specimens of malignant melanoma
    Steven Anderson
    Medical and Scientific Affairs, Roche Molecular Systems, Inc, 4300 Hacienda Dr, Pleasanton, CA 94588, USA
    Arch Pathol Lab Med 136:1385-91. 2012
  21. ncbi The IARC TP53 database: new online mutation analysis and recommendations to users
    Magali Olivier
    Molecular Carcinogenesis Group, International Agency for Research on Cancer, World Health Organization, Lyon, France
    Hum Mutat 19:607-14. 2002
    ..In addition, a new on-line application to retrieve somatic mutation data and analyze mutation patterns is now available. We also discuss limitations on the use of the database and provide recommendations to users...
  22. pmc Genome remodelling in a basal-like breast cancer metastasis and xenograft
    Li Ding
    The Genome Center at Washington University, St Louis, Missouri 63108, USA
    Nature 464:999-1005. 2010
    ..The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour...
  23. pmc Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi
    Catherine D Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T1Z3, Canada
    Nature 457:599-602. 2009
    ..Our results demonstrate an alternative route to MAP kinase activation in melanocytic neoplasia, providing new opportunities for therapeutic intervention...
  24. pmc Recurring mutations found by sequencing an acute myeloid leukemia genome
    Elaine R Mardis
    Department of Genetics, Washington University, St Louis, MO 63110, USA
    N Engl J Med 361:1058-66. 2009
    ..The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known...
  25. pmc Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders
    Christelle M Durand
    Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France
    Nat Genet 39:25-7. 2007
    ..These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders...
  26. ncbi Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations
    Margaret C Thompson
    St Jude Children s Research Hospital, Memphis, TN 38105, USA
    J Clin Oncol 24:1924-31. 2006
    ..We hypothesized that gene expression profiling might be a more rapid and cost-effective method of identifying tumors that contain specific genetic abnormalities...
  27. pmc JointSNVMix: a probabilistic model for accurate detection of somatic mutations in normal/tumour paired next-generation sequencing data
    Andrew Roth
    Department of Molecular Oncology, BC Cancer Agency, BC, Canada
    Bioinformatics 28:907-13. 2012
  28. pmc Benchmarking of mutation diagnostics in clinical lung cancer specimens
    Silvia Querings
    Max Planck Institute for Neurological Research with Klaus Joachim Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany
    PLoS ONE 6:e19601. 2011
    ..More broadly, our results emphasize the need for thorough evaluation of all mutation detection approaches against massively parallel sequencing as a prerequisite for any clinical implementation...
  29. pmc KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer
    F Loupakis
    Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Istituto Toscano Tumori and Department of Oncology, Transplantes and New Technologies in Medicine, University of Pisa, Via Roma 67 56126 Pisa, Italy
    Br J Cancer 101:715-21. 2009
    ..KRAS codons 12 and 13 mutations predict resistance to anti-EGFR monoclonal antibodies (moAbs) in metastatic colorectal cancer. Also, BRAF V600E mutation has been associated with resistance. Additional KRAS mutations are described in CRC...
  30. pmc A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration
    Gregory S Hageman
    Department of Ophthalmology and Visual Sciences, Cell Biology and Functional Genomics Laboratory, University of Iowa, Iowa City, IA 52240, USA
    Proc Natl Acad Sci U S A 102:7227-32. 2005
    ..We propose that genetic variation in a regulator of the alternative complement pathway, when combined with a triggering event, such as infection, underlie a major proportion of AMD in the human population...
  31. pmc mtDNA mutations increase tumorigenicity in prostate cancer
    John A Petros
    Department of Urology, Emory University, 1365A Clifton Road, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 102:719-24. 2005
    ..The mutant tumors also generated significantly more ROS. Therefore, mtDNA mutations do play an important role in the etiology of prostate cancer...
  32. pmc Profiling critical cancer gene mutations in clinical tumor samples
    Laura E MacConaill
    Center for Cancer Genome Discovery, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA
    PLoS ONE 4:e7887. 2009
    ..We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting...
  33. ncbi KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial
    Susan D Richman
    Leeds Institute of Molecular Medicine, St James s Institute of Oncology, Cancer Research UK Genomic Services, University of Leeds, Leeds, UK
    J Clin Oncol 27:5931-7. 2009
    ..We wanted to determine whether KRAS and/or BRAF mutation is also a predictive biomarker for other aCRC therapies...
  34. pmc Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy
    Yukiko K Hayashi
    Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
    J Clin Invest 119:2623-33. 2009
  35. ncbi High-resolution DNA melting analysis for simple and efficient molecular diagnostics
    Gudrun H Reed
    Department of Pathology, University of Utah Medical Center, 5B418, 50 North Medical Drive, Salt Lake City, UT 84132, USA
    Pharmacogenomics 8:597-608. 2007
    ..Owing to its simplicity and speed, the method is a good fit for personalized medicine as a rapid, inexpensive method to predict therapeutic response...
  36. ncbi Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines
    Antoinette Hollestelle
    Department of Medical Oncology, Josephine Nefkens Institute Be414, Erasmus MC, P O Box 1738, 3000 DR Rotterdam, The Netherlands
    Mol Cancer Res 5:195-201. 2007
    ..001). These results suggest that there is a fine distinction between the signaling activators and downstream effectors of the oncogenic PI3K and RAS pathways in breast epithelium and those in other tissues...
  37. pmc Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations
    Katherine A Janeway
    Department of Pediatric Hematology Oncology, Dana Farber Cancer Institute and Children s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:314-8. 2011
    ..Testing for germline mutations in SDH is recommended in patients with WT GIST. These findings highlight a potential central role of SDH dysregulation in WT GIST oncogenesis...
  38. ncbi Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence
    Tetsuya Mitsudomi
    Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1 1 Kanokoden, Chikusa ku, Nagoya 464 8681, Japan
    J Clin Oncol 23:2513-20. 2005
    ..To evaluate the relationship between mutations of the epidermal growth factor receptor (EGFR) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection...
  39. pmc Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing
    A Eliot Shearer
    Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 107:21104-9. 2010
    ..Massively parallel sequencing technologies provide sensitivity, specificity, and reproducibility at levels sufficient to perform genetic diagnosis of hearing loss...
  40. ncbi Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D
    H Bolz
    Institut fur Humangenetik, Universitatsklinikum Hamburg Eppendorf, Hamburg, Germany
    Nat Genet 27:108-12. 2001
    ..In an accompanying paper, it is shown that mutations in the mouse ortholog cause disorganization of inner ear stereocilia and deafness in the waltzer mouse...
  41. ncbi A gain-of-function mutation of JAK2 in myeloproliferative disorders
    Robert Kralovics
    Department of Research, Experimental Hematology, University Hospital Basel, Basel, Switzerland
    N Engl J Med 352:1779-90. 2005
    ..The loss of heterozygosity (LOH) on the short arm of chromosome 9 (9pLOH) in myeloproliferative disorders suggests that 9p harbors a mutation that contributes to the cause of clonal expansion of hematopoietic cells in these diseases...
  42. pmc Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production
    Aleksandra Trifunovic
    Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
    Proc Natl Acad Sci U S A 102:17993-8. 2005
    ..We propose instead that respiratory chain dysfunction per se is the primary inducer of premature aging in mtDNA mutator mice...
  43. ncbi Colorectal cancer: mutations in a signalling pathway
    D Williams Parsons
    The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, The Johns Hopkins University Medical Institutions, Baltimore, Maryland 21231, USA
    Nature 436:792. 2005
    ..The discovery of this mutational activation of a key cell-signalling pathway may provide new targets for therapeutic intervention...
  44. pmc Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032
    Jill C Rubinstein
    Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Transl Med 8:67. 2010
    ..Here we present evidence that a patient bearing the BRAF V600K mutation responded remarkably to PLX4032, suggesting that clinical trials should include all patients with activating BRAF V600E/K mutations...
  45. ncbi Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nat Genet 30:377-84. 2002
    ..The abrogation of the SF2/ASF-dependent ESE is the basis for inefficient inclusion of exon 7 in SMN2, resulting in the spinal muscular atrophy phenotype...
  46. ncbi Mutations in NOTCH1 cause aortic valve disease
    Vidu Garg
    Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9148, USA
    Nature 437:270-4. 2005
    ..These results suggest that NOTCH1 mutations cause an early developmental defect in the aortic valve and a later de-repression of calcium deposition that causes progressive aortic valve disease...
  47. pmc Whole-exome sequencing efficiently detects rare mutations in autosomal recessive nonsyndromic hearing loss
    Oscar Diaz-Horta
    John P Hussman Institute for Human Genomics and the Dr John T Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, United States of America
    PLoS ONE 7:e50628. 2012
    ..The excess of heterozygous variants should be considered during search for causative mutations in ARNSHL genes, especially in small-sized families...
  48. ncbi Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers
    P A Steck
    Department of Neuro Oncology, University of Texas, M D Anderson Cancer Center, Houston 77030, USA
    Nat Genet 15:356-62. 1997
    ..Our results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers...
  49. ncbi Detection of BRAF p.V600E mutations in melanomas: comparison of four methods argues for sequential use of immunohistochemistry and pyrosequencing
    Emeline Colomba
    EA4340, University of Versailles, Boulogne, France
    J Mol Diagn 15:94-100. 2013
    ..Pyrosequencing proved to be the most efficient method to detect BRAF mutations in melanomas and could be performed on VE1-negative or uninterpretable cases...
  50. ncbi The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder
    G S Stewart
    The University of Birmingham CRC Institute for Cancer Studies, The Medical School Edgbaston, United Kingdom
    Cell 99:577-87. 1999
    ..These data demonstrate that ATM and the hMre11/hRad50/Nbs1 protein complex act in the same DNA damage response pathway and link hMre11 to the complex pathology of A-T...
  51. ncbi Cancer: drivers and passengers
    Daniel A Haber
    Nature 446:145-6. 2007
  52. ncbi PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer
    Fotios Loupakis
    Department of Oncology, Azienda USL 6, Istituto Toscano Tumori, Livorno, Italy
    J Clin Oncol 27:2622-9. 2009
    ..This retrospective study investigated the role of PTEN loss, AKT phosphorylation, and KRAS mutations on the activity of cetuximab plus irinotecan in patients with metastatic colorectal cancer (mCRC)...
  53. pmc Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials
    Christine M Lovly
    Division of Hematology Oncology, Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
    PLoS ONE 7:e35309. 2012
  54. ncbi TLR4 mutations are associated with endotoxin hyporesponsiveness in humans
    N C Arbour
    1 Department of Medicine, Department of Veterans Affairs Medical Center, The University of Iowa, Iowa City, Iowa, USA
    Nat Genet 25:187-91. 2000
  55. ncbi Analytical performance of a real-time PCR-based assay for V600 mutations in the BRAF gene, used as the companion diagnostic test for the novel BRAF inhibitor vemurafenib in metastatic melanoma
    Harkanwal Halait
    Roche Molecular Diagnostics, Pleasanton, CA 94588, USA
    Diagn Mol Pathol 21:1-8. 2012
    ..A simple 1:2 dilution resulted in a valid test result of 76% in such cases. The cobas test is a reproducible assay that detects some non-V600E mutations and is more accurate than direct sequencing in detecting BRAFV600E...
  56. pmc Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A
    Anna M Jankowska
    Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
    Blood 118:3932-41. 2011
    ..Various mutant genotype combinations were observed, indicating molecular heterogeneity in CMML. Our results suggest that molecular defects affecting distinct pathways can lead to similar clinical phenotypes...
  57. pmc PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers
    Filip Janku
    Department of Investigational Cancer Therapeutics Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
    PLoS ONE 6:e22769. 2011
    ..Oncogenic mutations of PIK3CA, RAS (KRAS, NRAS), and BRAF have been identified in various malignancies, and activate the PI3K/AKT/mTOR and RAS/RAF/MEK pathways, respectively. Both pathways are critical drivers of tumorigenesis...
  58. ncbi Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer
    Toshimi Takano
    Division of Internal Medicine, National Cancer Center Hospital, 5 1 1 Tsukiji, Chuo Ku, Tokyo 104 0045, Japan
    J Clin Oncol 23:6829-37. 2005
    ..To evaluate epidermal growth factor receptor (EGFR) mutations and copy number as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC) receiving gefitinib...
  59. ncbi Identification and analysis of deleterious human SNPs
    Peng Yue
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville MD 20850, USA
    J Mol Biol 356:1263-74. 2006
    ..After carefully controlling for errors, we find that approximately one quarter of known non-synonymous SNPs are deleterious by these criteria, providing a set of possible contributors to human complex disease traits...
  60. pmc Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine
    Dora Dias-Santagata
    Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    EMBO Mol Med 2:146-58. 2010
    ..This work therefore establishes a platform for real-time targeted genotyping that can be widely adopted. We expect that efforts like this one will play an increasingly important role in cancer management...
  61. ncbi Spectrum of KIT/PDGFRA/BRAF mutations and Phosphatidylinositol-3-Kinase pathway gene alterations in gastrointestinal stromal tumors (GIST)
    Marc Daniels
    Institute of Pathology, University Erlangen, Germany
    Cancer Lett 312:43-54. 2011
    ..We suggest that BRAF mutations are of pathogenetic significance in wild type GISTs. The PI3K pathway should be assessed in future studies...
  62. ncbi American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy
    Vicki Leigh Keedy
    Vanderbilt University Medical Center, Nashville, TN, USA
    J Clin Oncol 29:2121-7. 2011
  63. pmc A rapid, sensitive, reproducible and cost-effective method for mutation profiling of colon cancer and metastatic lymph nodes
    Debora Fumagalli
    Department of Pathology, National Surgical Adjuvant Breast and Bowel Project, 1307 Federal St, Pittsburgh, PA 15212, USA
    BMC Cancer 10:101. 2010
    ..Our goal was to develop a high throughput, cost-effective and simple methodology for the detection of clinically relevant hot spot mutations in colon cancer...
  64. ncbi Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution
    Sohrab P Shah
    Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
    Nature 461:809-13. 2009
    ..Taken together, our data show that single nucleotide mutational heterogeneity can be a property of low or intermediate grade primary breast cancers and that significant evolution can occur with disease progression...
  65. ncbi Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene
    Y Miyoshi
    Department of Biochemistry, Cancer Institute, Tokyo, Japan
    Hum Mol Genet 1:229-33. 1992
    ..These results strongly suggest that somatic mutations of the APC gene are associated with development of a great majority of colorectal tumors...
  66. ncbi Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene
    D C Whitcomb
    Dept of Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA
    Nat Genet 14:141-5. 1996
    ..Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis...
  67. pmc Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome
    Veronique Fremeaux-Bacchi
    Service d Immunologie Biologique, Hopital Europeen Georges Pompidou, Paris, France
    Blood 112:4948-52. 2008
    ..We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS...
  68. ncbi The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer
    Magali Olivier
    IARC, Lyon, France
    Clin Cancer Res 12:1157-67. 2006
    ..These results, obtained on the largest series analyzed thus far, show that TP53 mutations identified by gene sequencing have an independent prognostic value in breast cancer and could have potential uses in clinical practice...
  69. ncbi PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas
    Jong Woo Lee
    Department of Pathology, College of Medicine, Catholic University of Korea, 505 Banpo Dong, Socho gu, Seoul 137 701, Korea
    Oncogene 24:1477-80. 2005
    ..The high incidence and wide distribution of PIK3CA gene mutation in the common human cancers suggest that alterations of lipid kinase pathway by PIK3CA mutations contribute to the development of human cancers...
  70. ncbi p53 mutations in human cancers
    M Hollstein
    Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
    Science 253:49-53. 1991
    ..These differences may reflect the etiological contributions of both exogenous and endogenous factors to human carcinogenesis...
  71. pmc Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans
    Joan C Marini
    Bone and Extracellular Matrix Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA
    Hum Mutat 28:209-21. 2007
    ..Our data on genotype-phenotype relationships indicate that the two collagen chains play very different roles in matrix integrity and that phenotype depends on intracellular and extracellular events...
  72. ncbi Defective myosin VIIA gene responsible for Usher syndrome type 1B
    D Weil
    Unité de Génétique Moléculaire Humaine URA CNRS 1968, Institut Pasteur, Paris, France
    Nature 374:60-1. 1995
    ..Thus USH1B appears as a primary cytoskeletal protein defect. These results implicate the genes encoding other unconventional myosins and their interacting proteins as candidates for other genetic forms of Usher syndrome...
  73. pmc Comparison of Sanger sequencing, pyrosequencing, and melting curve analysis for the detection of KRAS mutations: diagnostic and clinical implications
    Athanasios C Tsiatis
    The Johns Hopkins Medical Institutions, Department of Pathology, 600 N Wolfe Street, Park SB202, Baltimore, MD 21287, USA
    J Mol Diagn 12:425-32. 2010
    ..1% false positives and 6.1% false negatives. In our hands, the limit of detection for Sanger sequencing, pyrosequencing, and melting curve analysis was approximately 15 to 20%, 5%, and 10% mutant alleles, respectively...
  74. ncbi Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up
    Markku Miettinen
    Departments of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306 6000, USA
    Am J Surg Pathol 29:52-68. 2005
    ..The above results may be helpful for setting the criteria for adjuvant treatment such as Gleevec...
  75. ncbi OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28
    C Alexander
    Department of Molecular Genetics, Insititute of Ophthalmology, University College London, London, UK
    Nat Genet 26:211-5. 2000
    ..The presence of consensus signal peptide sequences suggests that the product of the gene OPA1 is targeted to mitochondria and may exert its function in mitochondrial biogenesis and stabilization of mitochondrial membrane integrity...
  76. ncbi Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib
    Gregory J Riely
    Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Clin Cancer Res 12:839-44. 2006
    ..We undertook this study to explore the relationship between EGFR mutation type and clinical variables, including treatment with gefitinib and erlotinib...
  77. pmc KIT as a therapeutic target in metastatic melanoma
    Richard D Carvajal
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    JAMA 305:2327-34. 2011
    ..We explored the effects of KIT inhibition using imatinib mesylate in this molecular subset of disease...
  78. ncbi Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy
    H Niimura
    Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    N Engl J Med 338:1248-57. 1998
    ..The spectrum of disease-causing mutations and the associated clinical features of these gene defects are unknown...
  79. pmc Identification of an acquired JAK2 mutation in polycythemia vera
    Runxiang Zhao
    Hematology Oncology Division, Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 280:22788-92. 2005
    ..This gain-of-function mutation of JAK may explain the hypersensitivity of PV progenitor cells to growth factors and cytokines. Our study thus defines a molecular defect of PV...
  80. pmc A multicenter blinded study to evaluate KRAS mutation testing methodologies in the clinical setting
    Vicki Whitehall
    Queensland Institute of Medical Research, Bancroft Building, 300 Herston Road, Herston Queensland 4029, Australia
    J Mol Diagn 11:543-52. 2009
    ..These results demonstrate that a variety of detection methodologies are suitable and provide comparable results for KRAS mutation analysis of clinical samples...
  81. ncbi Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy
    Kalliopi Pilichou
    Department of Biology, University of Padua Medical School, Padua, Italy
    Circulation 113:1171-9. 2006
    ..Therefore, desmoglein-2 (DSG2), the only desmoglein isoform expressed in cardiac myocytes, was screened in subjects with ARVC...
  82. ncbi VSX1: a gene for posterior polymorphous dystrophy and keratoconus
    Elise Heon
    Cellular and Molecular Division, Toronto Western Research Institute, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8
    Hum Mol Genet 11:1029-36. 2002
    ..These data define the molecular basis of two important corneal dystrophies and reveal the importance of the CVC domain in the human retina...
  83. ncbi Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib
    Sae Won Han
    Department of Internal Medicine, Seoul National University Hospital, Seoul, 110 744 Korea
    J Clin Oncol 23:2493-501. 2005
    ..This study was undertaken to investigate the effects of epidermal growth factor receptor (EGFR) mutation and its downstream signaling on response and survival in non-small-cell lung cancer (NSCLC) patients treated with gefitinib...
  84. ncbi High-throughput oncogene mutation profiling in human cancer
    Roman K Thomas
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nat Genet 39:347-51. 2007
    ..These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention...
  85. pmc Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high resolution melting analysis and ultra-deep pyrosequencing
    Emma Borràs
    Hospital de Terrassa, Ctra, Torrebonica, Terrassa, Spain
    BMC Cancer 11:406. 2011
    ..The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices...
  86. pmc Rapid identification of a disease allele in mouse through whole genome sequencing and bulk segregation analysis
    Carrie N Arnold
    Department of Genetics, Institute for Childhood and Neglected Disease, The Scripps Research Institute, La Jolla, California 92037, USA
    Genetics 187:633-41. 2011
    ..Our study demonstrates the speed and utility of whole genome sequencing coupled with low resolution meiotic mapping as a means of identifying causative mutations induced by ENU...
  87. ncbi Cross-validation study for epidermal growth factor receptor and KRAS mutation detection in 74 blinded non-small cell lung carcinoma samples: a total of 5550 exons sequenced by 15 molecular French laboratories (evaluation of the EGFR mutation status for th
    Michèle Beau-Faller
    Laboratoire de Biologie Moleculaire, Hopital de Hautepierre, Strasbourg, France
    J Thorac Oncol 6:1006-15. 2011
  88. ncbi PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma
    Lao H Saal
    Integrated Program in Cellular, Molecular, and Biophysical Studies, Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Cancer Res 65:2554-9. 2005
    ..Thus, mutation of PIK3CA is frequent, occurs early in carcinoma development, and has prognostic and therapeutic implications...
  89. ncbi Detection of EGFR mutation status in lung adenocarcinoma specimens with different proportions of tumor cells using two methods of differential sensitivity
    Hye Suk Han
    Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, South Korea
    J Thorac Oncol 7:355-64. 2012
    ..To evaluate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma specimens with different proportions of tumor cells using two methods with different sensitivities...
  90. ncbi High-resolution DNA melting analysis: advancements and limitations
    Carl T Wittwer
    Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
    Hum Mutat 30:857-9. 2009
  91. pmc Mutation analysis of congenital cataract in a Chinese family identified a novel missense mutation in the connexin 46 gene (GJA3)
    Zhou Zhou
    Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
    Mol Vis 16:713-9. 2010
    ..To identify the genetic defects in a three-generation Chinese family with congenital nuclear cataract...
  92. pmc Mutation analysis of CRYAA, CRYGC, and CRYGD associated with autosomal dominant congenital cataract in Brazilian families
    Alessandro Santana
    Cataract Service, Department of Ophthalmology, Faculty of Medical Sciences, Irmandade da Santa Casa de Misericordia de Sao Paulo, Sao Paulo, Brazil
    Mol Vis 15:793-800. 2009
    ..The purpose of this study was to investigate mutations in alphaA-crystallin (CRYAA), gammaC-crystallin (CRYGC), and gammaD-crystallin (CRYGD) in Brazilian families with nuclear and lamellar autosomal dominant congenital cataract...
  93. ncbi Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations
    Juergen Scharner
    Randall Division of Cell and Molecular Biophysics, King s College London, United Kingdom
    Hum Mutat 32:152-67. 2011
    ..Together, this study significantly augments the number of EDMD patients on the database and describes 15 novel mutations that underlie EDMD, which will contribute to establishing genotype-phenotype correlations...
  94. pmc Characterization of a novel mutation in the CRYBB2 gene associated with autosomal dominant congenital posterior subcapsular cataract in a Chinese family
    Ke Yao
    Eye Center of the 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China
    Mol Vis 17:144-52. 2011
    ..To identify the underlying genetic defect in four generations of a Chinese family affected with bilateral congenital posterior subcapsular cataracts...
  95. pmc Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23
    J M Bork
    Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA
    Am J Hum Genet 68:26-37. 2001
    ..A northern blot analysis of CDH23 showed a 9.5-kb transcript expressed primarily in the retina. CDH23 is also expressed in the cochlea, as is demonstrated by polymerase chain reaction amplification from cochlear cDNA...
  96. pmc Thrombomodulin mutations in atypical hemolytic-uremic syndrome
    Mieke Delvaeye
    VIB K U Leuven Vesalius Research Center, Leuven, Belgium
    N Engl J Med 361:345-57. 2009
    ..Genetic factors in the remaining cases are unknown. We studied the role of thrombomodulin, an endothelial glycoprotein with anticoagulant, antiinflammatory, and cytoprotective properties, in atypical hemolytic-uremic syndrome...
  97. ncbi Biomarkers of response to epidermal growth factor receptor inhibitors in Non-Small-Cell Lung Cancer Working Group: standardization for use in the clinical trial setting
    David A Eberhard
    Department of Pathology, Genentech Inc, San Francisco, CA, USA
    J Clin Oncol 26:983-94. 2008
    ..Recommendations for the standardization of molecular assays are also discussed...
  98. ncbi Comprehensive mutational screening in a cohort of Danish families with hereditary congenital cataract
    Lars Hansen
    Wilhelm Johannsen Centre for Functional Genome Research, Institute of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
    Invest Ophthalmol Vis Sci 50:3291-303. 2009
    ..Seven families have been published previously, and the data of the remaining 21 families are presented together with an overview of the results in all families...
  99. ncbi Leber congenital amaurosis - a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture
    Edwin M Stone
    Department of Ophthalmology, The University of Iowa College of Medicine, Carver Family Center for Macular Degeneration, Iowa City, IA 52242, USA
    Am J Ophthalmol 144:791-811. 2007
  100. pmc Accurate SNP and mutation detection by targeted custom microarray-based genomic enrichment of short-fragment sequencing libraries
    Michal Mokry
    Hubrecht Institute and University Medical Center Utrecht, KNAW, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Nucleic Acids Res 38:e116. 2010
    ..Raw sequencing data, alignment files and called SNPs have been submitted into GEO database http://www.ncbi.nlm.nih.gov/geo/ with accession number GSE18542...
  101. pmc Circulating mutant DNA to assess tumor dynamics
    Frank Diehl
    The Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center at the Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    Nat Med 14:985-90. 2008
    ..We suggest that this personalized genetic approach could be generally applied to individuals with other types of cancer...

Research Grants64

  1. Comprehensive NF1 Mutational Analysis in Leukemia Cells
    Ludwine Messiaen; Fiscal Year: 2006
    ..abstract_text> ..
  2. RBC Ion Transporters as Hemoglobinopathy Risk Modifiers
    Seth Alper; Fiscal Year: 2009
    ..The proposed experiments will increase understanding of sickle cell disease and thalassemia by providing mouse models for genetic tests of new drug therapies under development for near-term clinical testing. ..
    Michael Whyte; Fiscal Year: 2002
  4. Genetic Epidemiology of Parkinson's Disease
    Karen Marder; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  5. Safety of repetitive TMS in chronic subcortical stroke
    Steven Cramer; Fiscal Year: 2006
    ..The long-term goal of these studies is to develop a safe and efficacious method for facilitating motor cortex function in order to improve motor status of patients with stroke-related weakness. ..
  6. Safety of Autologous Marrow Stromal Cells After Stroke
    Steven Cramer; Fiscal Year: 2005
    ..This study is a Phase I safety trial, and thus represents the first step in evaluating autologous MSC transfusion in this regard. ..
    Daniel Link; Fiscal Year: 2006
    ..3. Examine the efficacy of stem cell mobilization to mediate tissue regeneration in a murine model of acute myocardial infarction. ..
  8. Molecular Pathogenesis of Severe Congential Neutropenia
    Daniel Link; Fiscal Year: 2008
    ..A novel xenotransplantation model of SCN will be developed to study hematopoiesis in vivo. ..
  9. Genetic analysis of congenital diaphragmatic hernia
    Anne Slavotinek; Fiscal Year: 2006
    ..abstract_text> ..
    Sydney Finkelstein; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  11. Analysis of Toxin A synthesis in P. aeruginosa
    Abdul Hamood; Fiscal Year: 2006
  12. Hereditary spastic paraplegia linked to chromosomes 8q
    Peter Hedera; Fiscal Year: 2006
    ..I will characterize the phenotype of transgenic animals. The study of a transgenic animal model will further enhance current state of knowledge about the pathophysiology of HSP and axonal degeneration. ..
  13. FMRI in Pre-Symptomatic PS1-related Alzheimer's Disease
    John Ringman; Fiscal Year: 2005
    ..UCI, with its strong dementia research program, growing MRI capabilities and opportunity to collaborate at the nearby UCLA Brain Imaging Center, is an excellent environment for this endeavor. ..
  14. Improving Waisman Center Animal Care Facility
    Albee Messing; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
    Leslie Lyons; Fiscal Year: 2007
    ..The rationale for this approach is that many primate researchers are unaware of the current primate resources and are unfamiliar with the use and advantages of genetics because it is outside their areas of expertise. ..
  16. Chemopreventive Actions of Equol Enantiomers
    Kenneth Setchell; Fiscal Year: 2007
    ..These studies are relevant to humans given the ammended health claim for soy and cancer risk-reduction currently being reviewed by the FDA. ..
  17. Pitx2 Function in Developing Mouse Brain Neurons
    Donna M Martin; Fiscal Year: 2010
    ..These results will help guide future experiments aimed at directing neural stem cell differentiation toward specific neuronal cell subtypes. ..
    Robert Grainger; Fiscal Year: 2008
    ..tropicalis. This project should complement the growing genomic resources for X. tropicalis which include a genome project to commence in the summer of 2002. ..
  19. Rapid Screen for Genotoxicants, Chemoprotectors, and Radioprotectors
    Stephen Dertinger; Fiscal Year: 2008
    ..In addition, this assay can be used to investigate agents designed to ameliorate the effects of radiation exposure, e.g. biological response modifiers. [unreadable] [unreadable] [unreadable] [unreadable]..
  20. High Accuracy Single Molecule DNA Sequencing by Synthesis
    John Thompson; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
    Christine Iacobuzio Donahue; Fiscal Year: 2008
    ..abstract_text> ..
  22. Disease pathogenesis of Noonan syndrome and related disorders
    Bruce Gelb; Fiscal Year: 2008
    ..Next, a candidate gene approach will be used to identify additional NS gene(s). This will be coupled with the use of human multiplex NS kindreds without PTPN11 mutations. ..
  23. Pathophysiologies Involving Hemostasis-related Genes
    Francis Castellino; Fiscal Year: 2008
    ..abstract_text> ..
  24. High Throughput Radiation Biodosimetry
    Stephen Dertinger; Fiscal Year: 2007
    ..We propose to develop such a radiation biodosimetry assay based on the extremely high analysis rates that are possible with flow cytometry instrumentation. [unreadable] [unreadable] [unreadable]..
  25. Long-term efficacy of pediatric HAART
    DALTON CHEKOKO WAMALWA; Fiscal Year: 2010
    ..This study will provide important information on effectiveness of HAART regimens being scaled up in resource-poor countries and help programs better plan for changes of drug regimens following treatment failure. ..
  26. Genetic Control of Early Retinal Development
    Robert M Grainger; Fiscal Year: 2010
    ..Third, we will examine the regulation of and interactions among a critical group of transcription factors essential for retina formation in order to ascertain their roles in the determination mechanism. ..
  27. Role of Pitx2 in the Mammalian Central Nervous System
    Donna Martin; Fiscal Year: 2005
    ..5-14.5) mouse diencephalon, 2) Develop and analyze mice with Pitx2 loss of function, and 3) Develop and analyze transgenic mice with CNS-specific Pitx2 gain of function. ..
  28. Feline Model of an Inherited Craniofacial Abnormality
    Leslie Lyons; Fiscal Year: 2004
    ..Once identified, mutation analyses of these genes in the cat or other species will lead to understanding the genetics of facial development in humans. ..
  29. Measuring Cytogenetic Damage in Human Blood
    Stephen Dertinger; Fiscal Year: 2003
    ..abstract_text> ..
  30. Anticancer drug resistance studies using Dictyostelium
    Stephen Alexander; Fiscal Year: 2003
    ..These studies will identify new mechanisms for drug resistance and new targets for chemotherapeutic intervention which can subsequently be validated in human cells. ..
  31. Diastolic Function in Hypertrophic Cardiomyopathy
    Carolyn Ho; Fiscal Year: 2003
    ..Such genotype-phenotype correlations have the potential to improve our ability to risk stratify and monitor patients, and may ultimately inspire noel approaches to management. ..
    Albee Messing; Fiscal Year: 2002
    ..In specific aim 3, he will test the hypothesis that formation of Rosenthal fibers in astrocytes is associated with fundamental physiological changes in astrocytes and in neuron-glial interactions. ..
  33. Mutation spectra in DNA repair-deficient backgrounds
    DEE DENVER; Fiscal Year: 2004
    ..abstract_text> ..
  34. A pharmacogenetic and pharmacodynamic study of erlotinib
    CHARLES RUDIN; Fiscal Year: 2004
    ..Defining the basis of this toxicity could also promote the development of EGFR-directed agents that may avoid such toxicity or that may be effective in a broader spectrum of cancer patients. ..
    Bruce Gelb; Fiscal Year: 2004
    ..Aside from illuminating one pathway toward the clinical endpoint of PDA, it will provide the starting place for identifying genes critical to ductal development that are activated by Char syndrome-related genes. ..
    Steven Cramer; Fiscal Year: 2003
    ..3) MGH-NMR Center (Charlestown, MA), located two miles from (1) and (2), is a pioneering fMRI center. ..
  37. TNF-Induced Apoptosis of Lymphocytes in Aged Humans
    Sudhir Gupta; Fiscal Year: 2004
    ..These studied should mechanism (s) for increased TNF-a-induced apoptosis during aging. ..
    Robert Grainger; Fiscal Year: 2001
    ..The final goal is to test the function of transcriptional regulatory genes in controlling lens competence, bias and specification in Xenopus embryos. ..
  39. Organization of the Trichromatic Cone Mosaic
    Joseph Carroll; Fiscal Year: 2005
    ..This will be done in subjects for whom we also have a representation of their cone mosaic, to be able to selectively stimulate cones from a particular class. ..
  40. In vivo mutation assay based on pig-a locus
    Stephen Dertinger; Fiscal Year: 2004
  41. 2001 International C. elegans Meeting
    Paul Sternberg; Fiscal Year: 2001
    ..Previous C. elegans meetings have led to the exchange of knowledge, ideas, methods, mutants, and clones, and have been vital in fostering the sense of excitement, collegiality and cooperativity that characterize this field. ..
    Robert Grainger; Fiscal Year: 2005
  43. Is a therapy for Alexander disease already FDA-approved?
    Albee Messing; Fiscal Year: 2006
    ..By restricting the focus to the FDA-approved list, successful identification of GFAP-suppressing drugs could offer immediate therapeutic benefit to Alexander disease patients. ..
  44. Soy Isoflavone Metabolite Equol--Formation and Fate
    Kenneth Setchell; Fiscal Year: 2008
    ..abstract_text> ..
  45. Phase I/II Study of MS-275 and 5-Azacytidine in Patients with Advanced Non-Small
    CHARLES RUDIN; Fiscal Year: 2008
    ..If successful, this approach could alter the poor prognosis of individuals with this disease. [unreadable] [unreadable] [unreadable]..
  46. Versatile Mutation Assay Platform
    Stephen Dertinger; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  47. Automation of the vitro Micronucleus Assay
    Stephen Dertinger; Fiscal Year: 2004
    ..abstract_text> ..
  48. Genetics and Pediatric Nonsyndromic Hearing Loss
    Margaret Kenna; Fiscal Year: 2005
    ..This information will be used to evaluate the effectiveness of genetic counseling associated with gene testing for deafness. ..
  49. Growth Factors and Colon Cancer
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention. ..
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..The AIAN cohort will serve as a resource to enhance research and training activities of AIAN students interested in health research, health education, and general public health. ..
  51. Aromatase Inhibitor in Males with Adrenal Hyperplasia
    Kyriakie Sarafoglou; Fiscal Year: 2006
    ..unreadable] [unreadable]..
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
    ..e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. ..
  53. Application of genomic approaches to classify retinoblastoma tumors
    Arupa Ganguly; Fiscal Year: 2008
    ..This will allow us to identify molecular signatures associated with risk of RB recurrence. [unreadable] [unreadable] [unreadable] [unreadable]..
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2003
    ..C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. ..
  55. Inhibitors of Yersinia Yop Type III Secretion(RMI)
    Joan Mecsas; Fiscal Year: 2005
    ..In addition, these inhibitors will be valuable tools to probe the structure and function of type III secretion systems encoded by Yersinia species and other Gram-negative bacterial pathogens. ..
    Hartmut Wohlrab; Fiscal Year: 2001
    ..The structure will permit the accurate localization of the functionally relevant residues and regions of PTP and should lead to a good understanding of transmembrane metabolite transport. ..
  57. Genetics of Survival of Yersinia pseudotuberculosis
    Joan Mecsas; Fiscal Year: 2002
    ..In addition, studies of yop mutant Yersinia strains in mouse strains with specific immune defects may indicate the facets of the immune system targeted by each Yop. ..
    PETER BURGERS; Fiscal Year: 2002
    ..Improper regulation of these processes in humans may lead to cancer. ..
    Kathleen Malone; Fiscal Year: 2002
    Seth Alper; Fiscal Year: 2007
    ..5. Define aspects of transcriptional and translational regulation of AE gene products in kidney of mutant and parental mouse strains and in cultured kidney cells. ..
    Ruth Ottman; Fiscal Year: 2007
    ..abstract_text> ..
  62. Sickle Red Cell K+ Transporter Genetics in S. cerevisiae
    Seth Alper; Fiscal Year: 2002
    ..3) (Provisional Aim): Time permitting, to improve, validate, and standardize growth rescue of trk1delta/trk2delta S. cerevisiae by expression in nonpermissive conditions of cDNA encoding the mammalian IK1 K(ca) channel. ..
    Joan Mecsas; Fiscal Year: 2007
    ..Our long-range goal is for these students to become independent scientists in academia or industry, and in this capacity, serve as mentors for other minority students. ..