gene amplification

Summary

Summary: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.

Top Publications

  1. ncbi Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene
    D J Slamon
    Science 235:177-82. 1987
  2. pmc The landscape of somatic copy-number alteration across human cancers
    Rameen Beroukhim
    Cancer Program and Medical and Population Genetics Group, The Broad Institute of M I T and Harvard, 7 Cambridge Center
    Nature 463:899-905. 2010
  3. ncbi Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer
    D J Slamon
    Department of Medicine, U C L A School of Medicine 90024
    Science 244:707-12. 1989
  4. ncbi Neuroblastoma: biological insights into a clinical enigma
    Garrett M Brodeur
    Division of Oncology, The Children s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania 19104 4318, USA
    Nat Rev Cancer 3:203-16. 2003
  5. ncbi Fibroblast growth factor signalling: from development to cancer
    Nicholas Turner
    Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London SW3 6JB, UK, and Royal Marsden Hospital, London SW3 6JJ, UK
    Nat Rev Cancer 10:116-29. 2010
  6. pmc Activating HER2 mutations in HER2 gene amplification negative breast cancer
    Ron Bose
    Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Cancer Discov 3:224-37. 2013
  7. pmc Gene amplification, ABC transporters and cytochrome P450s: unraveling the molecular basis of pyrethroid resistance in the dengue vector, Aedes aegypti
    Vassiliki Bariami
    Department of Biology, University of Crete, Haraklio, Greece
    PLoS Negl Trop Dis 6:e1692. 2012
  8. ncbi Genetic instabilities in human cancers
    C Lengauer
    Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA
    Nature 396:643-9. 1998
  9. ncbi Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations
    Guido Sauter
    Department of Pathology and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Ave, Ste 5409, Los Angeles, CA 90033
    J Clin Oncol 27:1323-33. 2009
  10. ncbi Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer
    Charles L Vogel
    University of Miami School of Medicine, Comprehensive Cancer Research Group Inc, and Columbia Cancer Research Network of Florida, Miami, FL, USA
    J Clin Oncol 20:719-26. 2002

Detail Information

Publications302 found, 100 shown here

  1. ncbi Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene
    D J Slamon
    Science 235:177-82. 1987
    ..HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors. Correlation of gene amplification with several disease parameters was evaluated...
  2. pmc The landscape of somatic copy-number alteration across human cancers
    Rameen Beroukhim
    Cancer Program and Medical and Population Genetics Group, The Broad Institute of M I T and Harvard, 7 Cambridge Center
    Nature 463:899-905. 2010
    ..Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types...
  3. ncbi Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer
    D J Slamon
    Department of Medicine, U C L A School of Medicine 90024
    Science 244:707-12. 1989
    ..The data presented further support the concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers...
  4. ncbi Neuroblastoma: biological insights into a clinical enigma
    Garrett M Brodeur
    Division of Oncology, The Children s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania 19104 4318, USA
    Nat Rev Cancer 3:203-16. 2003
    ..Future therapies will focus increasingly on the genes and biological pathways that contribute to malignant transformation or progression...
  5. ncbi Fibroblast growth factor signalling: from development to cancer
    Nicholas Turner
    Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London SW3 6JB, UK, and Royal Marsden Hospital, London SW3 6JJ, UK
    Nat Rev Cancer 10:116-29. 2010
    ....
  6. pmc Activating HER2 mutations in HER2 gene amplification negative breast cancer
    Ron Bose
    Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Cancer Discov 3:224-37. 2013
    ..cancer genome-sequencing projects identified 25 patients with HER2 somatic mutations in cancers lacking HER2 gene amplification. To determine the phenotype of these mutations, we functionally characterized 13 HER2 mutations using in ..
  7. pmc Gene amplification, ABC transporters and cytochrome P450s: unraveling the molecular basis of pyrethroid resistance in the dengue vector, Aedes aegypti
    Vassiliki Bariami
    Department of Biology, University of Crete, Haraklio, Greece
    PLoS Negl Trop Dis 6:e1692. 2012
    ..The near complete transcriptome of two pyrethroid resistant populations from the Caribbean was examined to explore the molecular basis of this resistance...
  8. ncbi Genetic instabilities in human cancers
    C Lengauer
    Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA
    Nature 396:643-9. 1998
    ..Recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis...
  9. ncbi Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations
    Guido Sauter
    Department of Pathology and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Ave, Ste 5409, Los Angeles, CA 90033
    J Clin Oncol 27:1323-33. 2009
    ..Conversely, gene amplification and FISH are significantly less dependent on tissue fixation methods, making this assay more reproducible ..
  10. ncbi Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer
    Charles L Vogel
    University of Miami School of Medicine, Comprehensive Cancer Research Group Inc, and Columbia Cancer Research Network of Florida, Miami, FL, USA
    J Clin Oncol 20:719-26. 2002
    ..To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer...
  11. ncbi Mutation of the PIK3CA gene in ovarian and breast cancer
    Ian G Campbell
    VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Cancer Res 64:7678-81. 2004
    ..0%) endometrioid and clear cell cancers, which was highly significant (P = 0.001). In contrast, PIK3CA gene amplification (>7-fold) was common among all histologic subtypes (24...
  12. ncbi The PIK3CA gene is mutated with high frequency in human breast cancers
    Kurtis E Bachman
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Department of Oncology, Baltimore, Maryland 21231, USA
    Cancer Biol Ther 3:772-5. 2004
    ..These results demonstrate that PIK3CA is the most mutated oncogene in breast cancer and support a role for PIK3CA in epithelial carcinogenesis...
  13. ncbi Gene amplification and adaptive evolution in bacteria
    Dan I Andersson
    Department of Medical Biochemistry and Microbiology, Uppsala, S 751 23, Sweden
    Annu Rev Genet 43:167-95. 2009
    ..Due to the high intrinsic instability and fitness costs associated with GDAs, they are generally transient in nature, and consequently their evolutionary and medical importance is often underestimated...
  14. ncbi Genomic and transcriptional aberrations linked to breast cancer pathophysiologies
    Koei Chin
    Comprehensive Cancer Center, 2340 Sutter Street, University of California, San Francisco, San Francisco, California 94143
    Cancer Cell 10:529-41. 2006
    ..Nine of these (FGFR1, IKBKB, ERBB2, PROCC, ADAM9, FNTA, ACACA, PNMT, and NR1D1) are considered druggable. Low-level CNAs appear to contribute to cancer progression by altering RNA and cellular metabolism...
  15. ncbi Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab
    M Tanner
    Laboratory of Cancer Biology, Institute of Medical Technology, University of Tampere and Tampere University Hospital, FIN 33101 Tampere, Finland
    Ann Oncol 16:273-8. 2005
    HER-2/neu gene amplification has predictive value in breast cancer patients responding to trastuzumab. We wanted to investigate the frequency and clinical significance of HER-2/neu amplification in gastric carcinoma.
  16. pmc FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer
    Nicholas Turner
    The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom
    Cancer Res 70:2085-94. 2010
    ..Our data suggest that amplification and overexpression of FGFR1 may be a major contributor to poor prognosis in luminal-type breast cancers, driving anchorage-independent proliferation and endocrine therapy resistance...
  17. ncbi Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma
    Levi A Garraway
    Department of Medical Oncology, and Melanoma Program in Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nature 436:117-22. 2005
    ..Together, these data suggest that MITF represents a distinct class of 'lineage survival' or 'lineage addiction' oncogenes required for both tissue-specific cancer development and tumour progression...
  18. pmc The MDM2 gene amplification database
    J Momand
    Department of Cell and Tumor Biology, Beckman Research Institute, National Medical Center, 1450 East Duarte Road, Duarte, CA 91010 3000, USA
    Nucleic Acids Res 26:3453-9. 1998
    ..The MDM2 gene has been shown to be abnormally up-regulated in human tumors and tumor cell lines by gene amplification, increased transcript levels and enhanced translation...
  19. pmc MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib
    Jochen K Lennerz
    Massachusetts General Hospital Harvard Medical School, Boston, MA 02114, USA
    J Clin Oncol 29:4803-10. 2011
    ..We examined a GEC cohort with follow-up and reported the clinical response of four additional patients with MET-amplified tumors to the small molecule inhibitor crizotinib as part of an expanded phase I cohort study...
  20. pmc 'Touchdown' PCR to circumvent spurious priming during gene amplification
    R H Don
    Centre for Molecular Biology and Biotechnology, University of Queensland, Brisbane, Australia
    Nucleic Acids Res 19:4008. 1991
  21. pmc Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer
    Amit Dutt
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, United States of America
    PLoS ONE 6:e20351. 2011
    ..Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma...
  22. ncbi KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer
    Astrid Lievre
    Universite Paris Descartes, Institut National de la Sante et de la Recherche Medicale UMR 775, Paris, France
    Cancer Res 66:3992-5. 2006
    ..The EGFR amplification, which is not as frequent as initially reported, is also associated with response to this treatment...
  23. pmc PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axis
    Nina Ilic
    Department of Cancer Biology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:E699-708. 2011
    ..Collectively, these findings suggest that analysis of drivers of protein translation could facilitate the identification of cancer lesions that confer resistance to PI3K pathway-targeted drugs...
  24. ncbi Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target
    Jeeyun Lee
    Division of Hematology Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
    Oncol Rep 25:1517-24. 2011
    ..However, the predictive role of MET amplification for treatment response should be further explored in upcoming clinical trials...
  25. ncbi Gene amplification in cancer
    Donna G Albertson
    Cancer Research Institute and Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA
    Trends Genet 22:447-55. 2006
    b>Gene amplification is a copy number increase of a restricted region of a chromosome arm. It is prevalent in some tumors and is associated with overexpression of the amplified gene(s)...
  26. ncbi Gene amplification and insecticide resistance
    Chris Bass
    Department of Biological Chemistry, Rothamsted Research, Harpenden, Herts, UK
    Pest Manag Sci 67:886-90. 2011
    ....
  27. ncbi Fibroblast growth factor receptor 1 gene amplification is associated with poor survival and cigarette smoking dosage in patients with resected squamous cell lung cancer
    Hye Ryun Kim
    Yonsei Cancer Center, Seoul, Korea
    J Clin Oncol 31:731-7. 2013
    ....
  28. ncbi Genomic amplification of MET with boundaries within fragile site FRA7G and upregulation of MET pathways in esophageal adenocarcinoma
    C T Miller
    Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Oncogene 25:409-18. 2006
    ..metaplasia, dysplasia, and EA revealed overexpression of the MET oncogene in EAs but only those with MET gene amplification. STS-amplification mapping revealed that the boundary of the MET amplicon in these EAs is defined by fragile ..
  29. pmc Integrated genome-wide DNA copy number and expression analysis identifies distinct mechanisms of primary chemoresistance in ovarian carcinomas
    Dariush Etemadmoghadam
    Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Clin Cancer Res 15:1417-27. 2009
    ..We analyzed somatic DNA copy number variation and gene expression data to identify key mechanisms associated with primary resistance in advanced-stage serous cancers...
  30. pmc HER-2 gene amplification can be acquired as breast cancer progresses
    Songdong Meng
    Cancer Immunobiology Center, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 101:9393-8. 2004
    ..Nine of 24 breast cancer patients whose primary tumor was HER-2-negative each acquired HER-2 gene amplification in their CTCs during cancer progression, i.e., 37.5% (95% confidence interval of 18.8-59.4%)...
  31. ncbi The pattern of gene amplification is determined by the chromosomal location of hairpin-capped breaks
    Vidhya Narayanan
    School of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
    Cell 125:1283-96. 2006
    DNA palindromes often colocalize in cancer cells with chromosomal regions that are predisposed to gene amplification. The molecular mechanisms by which palindromes can cause gene amplification are largely unknown...
  32. pmc Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752
    Gromoslaw A Smolen
    Cancer Center and Department of Pathology, Molecular Pathology Research Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 103:2316-21. 2006
    ..MET amplification may thus identify a subset of epithelial cancers that are uniquely sensitive to disruption of this pathway and define a patient group that is appropriate for clinical trials of targeted therapy using MET inhibitors...
  33. ncbi Overall genomic pattern is a predictor of outcome in neuroblastoma
    Isabelle Janoueix-Lerosey
    INSERM U830, Laboratoire de Génétique et Biologie des Cancers, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    J Clin Oncol 27:1026-33. 2009
    ..For a comprehensive overview of the genetic alterations of neuroblastoma, their association and clinical significance, we conducted a whole-genome DNA copy number analysis...
  34. ncbi Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer
    Francesco Graziano
    Azienda Ospedaliera Ospedali Riuniti Marche Nord 61122, Pesaro, Italy
    J Clin Oncol 29:4789-95. 2011
    ..To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain (CNG) or an activating truncation within a deoxyadenosine tract element (DATE) in the promoter region of the MET ligand HGF...
  35. ncbi Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer
    M M Tanner
    Laboratory of Cancer Genetics, Institute of Medical Technology, Tampere University and University Hospital, Finland
    Clin Cancer Res 6:1833-9. 2000
    ..5% of the sporadic tumors. The high frequency of gene amplification at 20q12-q13...
  36. pmc Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas
    Bas Kreike
    Division of Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Breast Cancer Res 9:R65. 2007
    ..One well-defined subtype of breast cancer is characterized by a lack of HER2 gene amplification and estrogen and progesterone receptor expression ('triple-negative tumors')...
  37. pmc BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation
    Ryan B Corcoran
    Massachusetts General Hospital Cancer Center, Boston, MA 02129, USA
    Sci Signal 3:ra84. 2010
    ..These findings implicate BRAF amplification as a mechanism of resistance to both MEK and BRAF inhibitors and suggest combined MEK and BRAF inhibition as a clinical strategy to overcome, or possibly prevent, this mechanism of resistance...
  38. ncbi Androgen receptor gene amplification and protein expression in recurrent prostate cancer
    O Harris Ford
    Department of Surgery, Division of Urology, University of North Carolina Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    J Urol 170:1817-21. 2003
    ..AR amplification may contribute to androgen receptor activation in relative androgen absence...
  39. pmc FGFR2 gene amplification and clinicopathological features in gastric cancer
    K Matsumoto
    Department of Genome Biology, Kinki University Faculty of Medicine, Osaka 589 8511, Japan
    Br J Cancer 106:727-32. 2012
    ..Frequency of FGFR2 amplification, its clinicopathological features, and the results of high-throughput screening assays in a large cohort of gastric clinical samples remain largely unclear...
  40. ncbi Amplification of the c-met, c-erbB-2 and epidermal growth factor receptor gene in human gastric cancers: correlation to clinical features
    K Tsugawa
    Department of Surgery II, Kanazawa University School of Medicine, Kanazawa, Japan
    Oncology 55:475-81. 1998
    ..Seven of the seventy cancers (10.0%) had c-met gene amplification, nine (12.9%) had c-erbB-2 gene amplification, and six (8.6%) had EGFR gene amplification, respectively...
  41. doi HER2 status and benefit from adjuvant trastuzumab in breast cancer
    Soonmyung Paik
    N Engl J Med 358:1409-11. 2008
  42. ncbi Amplification of a gene encoding a p53-associated protein in human sarcomas
    J D Oliner
    Department of Pediatrics, University of Michigan Cancer Center, Ann Arbor 48109
    Nature 358:80-3. 1992
    ..This mechanism of tumorigenesis parallels that for virally-induced tumours, in which viral oncogene products bind to and functionally inactivate p53...
  43. ncbi Prognostic relevance of gene amplifications and coamplifications in breast cancer
    Khawla Al-Kuraya
    King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
    Cancer Res 64:8534-40. 2004
    ..b>Gene amplification results in oncogene overexpression but may also serve as an indicator of genomic instability...
  44. pmc The Whole-genome sequencing of the obligate intracellular bacterium Orientia tsutsugamushi revealed massive gene amplification during reductive genome evolution
    Keisuke Nakayama
    Division of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kiyotake, Miyazaki, Japan
    DNA Res 15:185-99. 2008
    ..tsutsugamushi and the pathogenesis of 'Tsutsugamushi' disease...
  45. pmc Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer
    J Edwards
    Endocrine Cancer Group, Surgical and Translational research section, Division of Cancer Sciences and Molecular Pathology, Glasgow Royal Infirmary, Glasgow G31 2ER, Scotland
    Br J Cancer 89:552-6. 2003
    This study examined androgen receptor (AR) gene amplification and protein expression in 102 matched paired hormone sensitive and resistant tumours from 51 patients...
  46. pmc Molecular cytogenetic analysis of 11 new breast cancer cell lines
    F Forozan
    Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 4470, USA
    Br J Cancer 81:1328-34. 1999
    ..In summary, this set of breast cancer cell lines displaying prominent DNA amplifications should facilitate discovery and functional analysis of genes and signal transduction pathways contributing to breast cancer development...
  47. ncbi Molecular characterization of breast cancer with high-resolution oligonucleotide comparative genomic hybridization array
    Fabrice Andre
    Translational Research Unit, UPRES03535, Paris Sud University, Orsay, France
    Clin Cancer Res 15:441-51. 2009
    ..We used high-resolution oligonucleotide comparative genomic hybridization (CGH) arrays and matching gene expression array data to identify dysregulated genes and to classify breast cancers according to gene copy number anomalies...
  48. pmc In silico identification of gene amplification targets for improvement of lycopene production
    Hyung Seok Choi
    Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering BK21 Program, KAIST, Daejeon 305 701, Republic of Korea
    Appl Environ Microbiol 76:3097-105. 2010
    ..Here, we report a strategy called flux scanning based on enforced objective flux (FSEOF) to identify gene amplification targets...
  49. ncbi Does chromosome 17 centromere copy number predict polysomy in breast cancer? A fluorescence in situ hybridization and microarray-based CGH analysis
    Caterina Marchio
    The Breakthrough Breast Cancer Research Centre Institute of Cancer Research, London, UK
    J Pathol 219:16-24. 2009
    ..0 in FISH analysis is frequently related to gain or amplification of the centromeric region. Larger studies investigating the genetic profiles of CEP17 polysomic cases are warranted...
  50. pmc High-resolution genomic and expression analyses of copy number alterations in HER2-amplified breast cancer
    Johan Staaf
    Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, Lund, Sweden
    Breast Cancer Res 12:R25. 2010
    HER2 gene amplification and protein overexpression (HER2+) define a clinically challenging subgroup of breast cancer with variable prognosis and response to therapy...
  51. pmc MET expression and amplification in patients with localized gastric cancer
    Yelena Y Janjigian
    Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, New York, NY 10065, USA
    Cancer Epidemiol Biomarkers Prev 20:1021-7. 2011
    MET, the receptor for hepatocyte growth factor, has been proposed as a therapeutic target in gastric cancer. This study assessed the incidence of MET expression and gene amplification in tumors of Western patients with gastric cancer.
  52. pmc Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer
    Jeffrey A Engelman
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA
    J Clin Invest 116:2695-706. 2006
    ....
  53. pmc EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer
    Adrian P Bracken
    European Institute of Oncology, Department of Experimental Oncology, Via Ripamonti 435, 20141 Milan, Italy
    EMBO J 22:5323-35. 2003
    ....
  54. ncbi Induction of gene amplification as a gain-of-function phenotype of mutant p53 proteins
    Sally El-Hizawi
    Department of Dermatology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA
    Cancer Res 62:3264-70. 2002
    b>Gene amplification accompanies tumor progression and is involved in the development of drug resistance. Previously, we reported (A. Albor et al., Cancer Res...
  55. pmc Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum
    Philippe Leprohon
    Centre de Recherche en Infectiologie et Division de Microbiologie, Universite Laval, Quebec, Canada
    Nucleic Acids Res 37:1387-99. 2009
    ..Selection of a partial revertant line correlated antimomy resistance levels and the copy number of aneuploid chromosomes, suggesting a putative link between aneuploidy and drug resistance in Leishmania...
  56. ncbi Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients
    Marta Pestrin
    Translational Research Unit c o Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Piazza dell Ospedale 2, 59100, Prato, Italy
    Breast Cancer Res Treat 118:523-30. 2009
    ..278). Our study suggests that a subset of patients with HER2-negative primary tumors develops HER2-positive CTCs during disease progression...
  57. pmc Intrastrand annealing leads to the formation of a large DNA palindrome and determines the boundaries of genomic amplification in human cancer
    Hisashi Tanaka
    Fred Hutchinson Cancer Reserach Center, Seattle, WA 98109, USA
    Mol Cell Biol 27:1993-2002. 2007
    Amplification of large chromosomal regions (gene amplification) is a common somatic alteration in human cancer cells and often is associated with advanced disease...
  58. ncbi Molecular biology of neuroblastoma
    J M Maris
    Division of Oncology, Children s Hospital of Philadelphia, Philadelphia, PA 19104 4318, USA
    J Clin Oncol 17:2264-79. 1999
    ..Alterations in the expression of genes that regulate apoptosis also correlate with neuroblastoma behavior and may help to explain the phenomenon of spontaneous regression observed in a well-defined subset of patients...
  59. ncbi Association between gain-of-function mutations in PIK3CA and resistance to HER2-targeted agents in HER2-amplified breast cancer cell lines
    Y Kataoka
    Hospital Pharmacy, National Cancer Hospital East, Kashiwa, Japan
    Ann Oncol 21:255-62. 2010
    ..We investigated the influence of PIK3CA mutations on sensitivity to HER2-targeted agents in naturally derived breast cancer cells...
  60. ncbi MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas
    Sang Y Ha
    Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    Mod Pathol 26:1632-41. 2013
    ..Further in situ hybridization confirmed the presence of MET gene amplification. Among the 495 gastric cancers, simultaneous membranous and cytoplasmic overexpression of MET was found in ..
  61. pmc Association of HER2/ErbB2 expression and gene amplification with pathologic features and prognosis in esophageal adenocarcinomas
    Harry H Yoon
    Departments of Medical Oncology, Health Sciences Research, Cytogenetics, Anatomic Pathology, Cancer Center, Laboratory Medicine and Pathology, and Gastroenterology, Mayo Clinic, Rochester, MN 55905, USA
    Clin Cancer Res 18:546-54. 2012
    We examined the frequency, tumor characteristics, and prognostic impact of HER2 protein expression and gene amplification in patients with curatively resected esophageal adenocarcinoma (EAC).
  62. pmc Effects of cyclin D1 gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study
    Katja Lundgren
    Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Malmo University Hospital, SE 205 02 Malmo, Sweden
    Breast Cancer Res 14:R57. 2012
    b>Gene amplification of CCND1 is observed in a subgroup of breast cancers with poor prognosis, whereas overexpression of the protein cyclin D1 has been linked to both worse and better clinical outcome...
  63. ncbi Compensatory gene amplification restores fitness after inter-species gene replacements
    Peter A Lind
    Department of Medical Biochemistry and Microbiology, Uppsala University, SE 75123 Uppsala, Sweden
    Mol Microbiol 75:1078-89. 2010
    ..However, these fitness defects could be partially ameliorated by gene amplification that augmented the dosage of the heterologous proteins...
  64. ncbi The SRY-HMG box gene, SOX4, is a target of gene amplification at chromosome 6p in lung cancer
    Pedro P Medina
    Lung Cancer Group, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncologicas CNIO, Madrid, Spain
    Hum Mol Genet 18:1343-52. 2009
    ..To identify novel oncogenes, activated by gene amplification, we analyzed cDNA microarrays by high-resolution comparative genome hybridization and compared DNA copy ..
  65. pmc p53 is a direct transcriptional target of MYCN in neuroblastoma
    Lindi Chen
    Northern Institute for Cancer Research, Newcastle University, Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne NE2 4H, United Kingdom
    Cancer Res 70:1377-88. 2010
    ..We concluded that MYCN transcriptionally upregulates p53 in neuroblastoma and uses p53 to mediate a key mechanism of apoptosis...
  66. ncbi EGFR protein overexpression and gene amplification in squamous cell carcinomas of the esophagus
    Mitsuhiko Hanawa
    Department of Pathology, School of Medicine, University of Yamanashi, Japan
    Int J Cancer 118:1173-80. 2006
    ..of epidermal growth factor receptor (EGFR) is observed in many cancers, sometimes accompanied by gene amplification. Recently, several clinical therapies targeting EGFR were developed, but the eligibility criteria for these ..
  67. ncbi HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas
    M F Press
    Norris Comprehensive Cancer Center and Department of Pathology, University of Southern California School of Medicine, Los Angeles, CA 90033, USA
    J Clin Oncol 15:2894-904. 1997
    ..was performed to validate fluorescence in situ hybridization (FISH) as a sensitive and specific method for assessing HER-2/neu gene amplification in archival tissue and to test whether this alteration is associated with poor prognosis.
  68. ncbi The role of MYCN in the failure of MYCN amplified neuroblastoma cell lines to G1 arrest after DNA damage
    Emma Bell
    Northern Institute for Cancer Research, University of Newcastle upon Tyne, Newcastle upon Tyne, UK
    Cell Cycle 5:2639-47. 2006
    ..This study is the first to determine that MNA correlates with a failure to G1 arrest and attenuated p21(WAF1) induction; however MYCN expression alone is not causally responsible...
  69. ncbi Amplicons on chromosome 12q13-21 in glioblastoma recurrences
    Ulrike Fischer
    Department of Human Genetics, Saarland University, 66421 Homburg Saar, Germany
    Int J Cancer 126:2594-602. 2010
    ..We recognized a significant longer survival time in glioblastoma patients that lack amplifications of either CDK4, CYP27B1, XRCC6BP1 (KUB3), or MDM2...
  70. pmc Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients
    J D Barros-Silva
    Department of Genetics, Portuguese Oncology Institute, Porto, Portugal
    Br J Cancer 100:487-93. 2009
    ....
  71. ncbi Expression of fragile sites triggers intrachromosomal mammalian gene amplification and sets boundaries to early amplicons
    A Coquelle
    Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France
    Cell 89:215-25. 1997
    Drug-selected intrachromosomal gene amplification by breakage-fusion-bridge (BFB) cycles is well documented in mammalian cells, but factors governing this mechanism are not clear...
  72. ncbi Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer
    P Koivisto
    Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere, Finland
    Cancer Res 57:314-9. 1997
    ..28%) of the recurrent therapy-resistant tumors, but none of the untreated primary tumors, contained AR gene amplification as determined by fluorescence in situ hybridization...
  73. pmc High-resolution array copy number analyses for detection of deletion, gain, amplification and copy-neutral LOH in primary neuroblastoma tumors: four cases of homozygous deletions of the CDKN2A gene
    Helena Caren
    Department of Clinical Genetics, Institute of Biomedicine, Goteborg University, Sahlgrenska University Hospital, SE 41345 Goteborg, Sweden
    BMC Genomics 9:353. 2008
    ..We have used array-based copy number analysis using oligonucleotide single nucleotide polymorphisms (SNP) arrays to analyze the chromosomal structure of a large number of neuroblastoma tumors of different clinical and biological subsets...
  74. ncbi Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes
    Gopeshwar Narayan
    Department of Pathology, Columbia University Medical Center, NY 10032, USA
    Genes Chromosomes Cancer 46:373-84. 2007
    ..These data, thus, form an important step toward the identification of biologically relevant genes in CC pathogenesis. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat...
  75. ncbi Gene amplification CCNE1 is related to poor survival and potential therapeutic target in ovarian cancer
    Naomi Nakayama
    Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan
    Cancer 116:2621-34. 2010
    ..This study examined the clinical significance of CCNE1 (Cyclin E1) amplification and assessed whether CCNE1 is a potential therapeutic target in ovarian cancer...
  76. ncbi Human papillomavirus infection and cyclin D1 gene amplification in laryngeal squamous cell carcinoma: biologic function and clinical significance
    Giovanni Almadori
    Istituto di Clinica Otorinolaringoiatria, Policlinico Agostino Gemelli, Largo Agostino Gemelli, 00168, Roma, Italy
    Head Neck 24:597-604. 2002
    ..Cyclin D1 gene (CCND1) overexpression and amplification have been shown to play a role as prognostic factors in many human cancers, among which are head and neck cancers...
  77. ncbi Prognostic significance of gene expression profiles of metastatic neuroblastomas lacking MYCN gene amplification
    Shahab Asgharzadeh
    Department of Pediatrics, Division of Hematology Oncology, Childrens Hospital Los Angeles and Saban Research Institute, University of Southern California, Los Angeles, CA, USA
    J Natl Cancer Inst 98:1193-203. 2006
    The aggressiveness of metastatic neuroblastomas that lack MYCN gene amplification varies with age--they are least aggressive when diagnosed in patients younger than 12 months and most aggressive when diagnosed in patients older than 24 ..
  78. ncbi Sequence mutations and amplification of PIK3CA and AKT2 genes in purified ovarian serous neoplasms
    Kentaro Nakayama
    Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    Cancer Biol Ther 5:779-85. 2006
    ..were isolated from high-grade ovarian serous carcinomas and serous borderline tumors (SBTs) and assessed gene amplification using a dual-color FISH on tissue microarrays...
  79. pmc Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesis
    S S Kwek
    Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143 0808, USA
    Oncogene 28:1892-903. 2009
    ....
  80. ncbi Isolation of a novel candidate oncogene within a frequently amplified region at 3q26 in ovarian cancer
    X Y Guan
    Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong
    Cancer Res 61:3806-9. 2001
    ..The proliferation-related function of eIF-5A supports that eIF-5A2 is a candidate oncogene related to the development of ovarian cancer...
  81. pmc A mechanism of palindromic gene amplification in Saccharomyces cerevisiae
    Alison J Rattray
    Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute Frederick Cancer Research and Development Center, Maryland 21702, USA
    Genes Dev 19:1390-9. 2005
    Selective gene amplification is associated with normal development, neoplasia, and drug resistance...
  82. ncbi Bacterial gene amplification: implications for the evolution of antibiotic resistance
    Linus Sandegren
    Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, Uppsala, S751 23, Sweden
    Nat Rev Microbiol 7:578-88. 2009
    ..In this Review, we highlight the dynamic properties of gene amplifications and describe how they can facilitate adaptive evolution in response to toxic drugs...
  83. pmc ZNF703 gene amplification at 8p12 specifies luminal B breast cancer
    Fabrice Sircoulomb
    Laboratoire d Oncologie Moleculaire, Centre de Recherche en Cancerologie de Marseille, INSERM, U891, Institut Paoli Calmettes, Marseille, France
    EMBO Mol Med 3:153-66. 2011
    ..Moreover, we show that ZNF703 is implicated in the regulation of ER and E2F1 transcription factor. These findings point out the prominent role of ZNF703 in transcription modulation, stem cell regulation and luminal B oncogenesis...
  84. pmc Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequent genetic changes in cervical carcinoma
    Pulivarthi H Rao
    Texas Children s Cancer Center, Baylor College of Medicine, Houston, TX, USA
    BMC Cancer 4:5. 2004
    ..Therefore, genetic characterization is essential for understanding the biology and clinical heterogeneity in cervical cancer (CC)...
  85. ncbi PIK3CA gene amplification in Japanese non-small cell lung cancer
    Osamu Kawano
    Lung Cancer 58:159-60. 2007
    ..Among 11 patients with PIK3CA amplification, two patients harbored a PIK3CA mutation. There was significant difference in survival between the patients with PIK3CA normal copy number and the patients with PIK3CA amplification...
  86. ncbi Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines
    Z Q Yang
    Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Japan
    Cancer Res 60:4735-9. 2000
    ..Our findings suggest that overexpressed GASC1 may play an important role in the development and/or progression of various types of cancer including ESC...
  87. ncbi Alterations of chromosomal copy number during progression of diffuse-type gastric carcinomas: metaphase- and array-based comparative genomic hybridization analyses of multiple samples from individual tumours
    Dun Fa Peng
    First Department of Pathology, Shiga University of Medical Science, Otsu, 520 2192, Japan
    J Pathol 201:439-50. 2003
    ....
  88. ncbi SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer
    Theresia Wilbertz
    Institute of Pathology, Comprehensive Cancer Center, University Hospital Tuebingen, Tuebingen, Germany
    Mod Pathol 24:944-53. 2011
    ..In conclusion, SOX2 amplification and upregulation are frequent events in squamous cell carcinomas of the lung and are associated with indicators of favorable prognosis...
  89. ncbi Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas
    Christine H Chung
    Division of Hematology Oncology, Department of Medicine, Vanderbilt Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 6307, USA
    J Clin Oncol 24:4170-6. 2006
    ..A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC...
  90. ncbi Amplification and overexpression of E2F3 in human bladder cancer
    Andrew Feber
    Section of Molecular Carcinogenesis and Male Urological Cancer Research, Centre, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
    Oncogene 23:1627-30. 2004
    ..When considered together with the established role of E2F3 in cell cycle progression, these results suggest that the E2F3 gene represents a candidate bladder cancer oncogene that is activated by DNA amplification and overexpression...
  91. ncbi Palindromic gene amplification--an evolutionarily conserved role for DNA inverted repeats in the genome
    Hisashi Tanaka
    Department of Molecular Genetics, Cleveland Clinic Lerner Research Institute, 9, 500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nat Rev Cancer 9:216-24. 2009
    The clinical importance of gene amplification in the diagnosis and treatment of cancer has been widely recognized, as it is often evident in advanced stages of diseases. However, our knowledge of the underlying mechanisms is still limited...
  92. pmc Gene amplification as double minutes or homogeneously staining regions in solid tumors: origin and structure
    Clelia Tiziana Storlazzi
    Department of Genetics and Microbiology, University of Bari, Bari 70126, Italy
    Genome Res 20:1198-206. 2010
    ..Fusion transcripts involving NBAS (also known as NAG), FAM49A, BC035112 (also known as NCRNA00276), and SMC6 genes were indeed detected, although their role in the context of the tumor is not clear...
  93. ncbi MET and KRAS gene amplification mediates acquired resistance to MET tyrosine kinase inhibitors
    Virna Cepero
    Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Turin, Italy
    Cancer Res 70:7580-90. 2010
    ..Resistant cells displayed MET gene amplification, leading to increased expression and constitutive phosphorylation of MET, followed by subsequent ..
  94. ncbi PIK3CA amplification is predictive of poor prognosis in Tunisian patients with nasopharyngeal carcinoma
    Ali Fendri
    Laboratory of Cancer Genetic and Production of Recombinant Proteins, Route Sidi, Mansour Sfax, Sfax, Tunisia
    Cancer Sci 100:2034-9. 2009
    ..screen for PIK3CA mutations in the two hot spot regions (exons 9 and 20) and to investigate for the PIK3CA gene amplification combined with the expression analysis of the phosphorylated Akt (pAkt)...
  95. ncbi Microevolution of Cryptococcus neoformans driven by massive tandem gene amplification
    Eve W L Chow
    Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia
    Mol Biol Evol 29:1987-2000. 2012
    ..these ~40-kb regions of the human fungal pathogen Cryptococcus neoformans, we have identified a recent gene amplification event near the right telomere of chromosome 3 that involves a gene encoding an arsenite efflux transporter (..
  96. ncbi Exploiting the PI3K/AKT pathway for cancer drug discovery
    Bryan T Hennessy
    Department of Molecular Therapeutics, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    Nat Rev Drug Discov 4:988-1004. 2005
    ..This warrants exploiting the PI3K/AKT pathway for cancer drug discovery...
  97. ncbi FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival
    Kaiko Kunii
    Pharmacology, Merck Research Laboratories, Boston, MA 02115, USA
    Cancer Res 68:2340-8. 2008
    ..Inhibitors of FGFR2 or Erbb3 signaling may have therapeutic efficacy in the subset of gastric cancers containing FGFR2 amplification...
  98. ncbi Age-dependent accumulation of genomic aberrations and deregulation of cell cycle and telomerase genes in metastatic neuroblastoma
    Simona Coco
    Department of Advanced Diagnostic Technologies IRCCS AOU San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
    Int J Cancer 131:1591-600. 2012
    ..The higher DNA instability observed in G3/MYCN- NBs than in MYCN-amplified G3 may also explain why patients ≥ 19 months have a poor outcome independently by MYCN status...
  99. pmc A novel gene amplification system in yeast based on double rolling-circle replication
    Takaaki Watanabe
    Department of Molecular Biomechanics, School of Life Science, The Graduate University for Advanced Studies Sokendai, Myodaiji, Okazaki, Japan
    EMBO J 24:190-8. 2005
    b>Gene amplification is involved in various biological phenomena such as cancer development and drug resistance. However, the mechanism is largely unknown because of the complexity of the amplification process...
  100. ncbi Extrachromosomal double minutes and chromosomal homogeneously staining regions as probes for chromosome research
    N Shimizu
    Graduate School of Biosphere Science, Hiroshima University, Higashi Hiroshima, Japan
    Cytogenet Genome Res 124:312-26. 2009
    b>Gene amplification in human cancer cells generates two cytogenetically identifiable structures: extrachromosomal double minutes (DMs) and the chromosomal homogeneously staining region (HSR)...
  101. ncbi Simultaneous detection of TOP2A and HER2 gene amplification by multiplex ligation-dependent probe amplification in breast cancer
    Cathy B Moelans
    Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
    Mod Pathol 23:62-70. 2010
    HER-2/neu gene amplification, found in certain subtypes of (breast-) cancers, is an independent prognostic factor of poor outcome and determines eligibility for systemic treatment with trastuzumab...

Research Grants66

  1. BIOCHEMISTRY OF PRE-MRNA SPLICING
    Adrian R Krainer; Fiscal Year: 2010
    ..For example, the gene encoding the splicing factor SF2/ASF is a proto-oncogene that can be activated by gene amplification in breast cancer. Drugs are being developed to correct aberrant splicing, e.g...
  2. Screening Complete TB Proteome for Protective Antigens
    Alan Greener; Fiscal Year: 2010
    ..The high throughput process that was developed combines efficient gene amplification and protein expression methods with serum- and splenocyte-based assays to determine the level of antibody- ..
  3. Structure and Function of the Hepatitis C Virus Genome
    Peter Sarnow; Fiscal Year: 2013
    ..This application will study two important HCV RNA-protein interactions that regulate HCV gene amplification. A highly-structured RNA element is located in the viral 5'noncoding region that functions as an ..
  4. Developing miRNA diagnostic methods and identifying tumor regulatory networks
    Thomas Tuschl; Fiscal Year: 2010
    ..will apply our methods to assess the value of miRNA analysis in a large collection of triple negative (HER2 gene amplification, Estrogen Receptor (ER), and Progesterone Receptor (PR) negative) and other types of breast tumors in ..
  5. CSHL Eukaryotic DNA Replication Conference
    David J Stewart; Fiscal Year: 2013
    ..a diverse array of topics, systems, and approaches including studies of: (1) chromosomal replication and gene amplification in organisms as diverse as yeast, Drosophila, Xenopus and mammalian cells;(2) the replication of viral ..
  6. 2011 EUKARYOTIC DNA REPLICATION &GENOME MAINTENANCE
    David J Stewart; Fiscal Year: 2011
    ..a diverse array of topics, systems, and approaches including studies of: (1) chromosomal replication and gene amplification in organisms as diverse as yeast, Drosophila, Xenopus and mammalian cells;(2) the replication of viral ..
  7. TARGETING ONCOGENE EXPRESSION TO SKIN IN TRANSGENIC MICE
    DENNIS ROOP; Fiscal Year: 2013
    ..Aurora-A targets wild type p53 signaling, while SCCs that form in GOF p53 mice are defined by both Myc gene amplification and by deregulation of Aurora-A...
  8. Transcriptomics and Population Genetics of Mosquito Resistance to Pyrethroids
    Mariangela Bonizzoni; Fiscal Year: 2013
    ..In particular, gene amplification-based techniques have allowed the identification of point mutations in coding regions of the para-type ..
  9. The Role of miR-17~92 in Autoimmune Diseases
    Changchun Xiao; Fiscal Year: 2013
    ..which encodes six distinct miRNAs, and the elevated expression of miR-17~92 miRNAs in cells carrying this gene amplification. We have generated a miR-17~92 transgene whose expression can be turned on conditionally by Cre recombinase ..
  10. The role of DEK in breast cancer development and therapy
    LISA MARIE PRIVETTE VINNEDGE; Fiscal Year: 2010
    ..However, its oncogenic activities in vivo remain poorly understood. Gene amplification and upregulated mRNA expression have been described for the human DEK gene in hematopoietic cancers and ..
  11. Wavefront Corrected Multimodal Optical Coherence and Two-Photon Microscopy for Ra
    Yuankai Kenny Tao; Fiscal Year: 2012
    ..and collagen orientation, as well as exogenous contrast sensitive to cytokeratins, hormone receptors, and gene amplification. The utility of OCM-TPM, relative to standard immunohistochemistry, will be assessed in a clinical setting ..
  12. Novel mechanism of neuroprotection against neurotoxins
    Jianhua Zhang; Fiscal Year: 2012
    ..a-syn gene amplification is responsible for a small subset of familial PD...
  13. Dual Targeting of DNA Repair and p53 pathways for treatment of brain cancer
    KAREN ELIZABETH POLLOK; Fiscal Year: 2013
    ..of established glioblastoma cell lines and early passaged glioblastoma primary cultures that differ in EGFR gene amplification, p53 status (wild-type or mutant), HDM2 status, MGMT expression, and sensitivities to TMZ and irradiation ..
  14. The Role of Cul4A in Genome Stability and Cancer Development
    Liang You; Fiscal Year: 2013
    ..The gain-of-function effect of gene amplification makes them ideal therapeutic targets for cancer...
  15. Selenium as an adjuvant to imatinib therapy
    Alan Diamond; Fiscal Year: 2010
    ..Resistance most often develops due to the appearance of secondary point mutations in the ABL gene or by gene amplification, rendering imatinab treatment ineffective...
  16. Regulation of cell homeostasis by fbx4
    JOHN ALAN DIEHL; Fiscal Year: 2013
    ..While cyclin D1 overexpression is a consequence of gene amplification and chromosome translocation in a subset of cancers, decreased cyclin D1 protein degradation, which depends ..
  17. HER3 Signaling in Development and Cancer of the Breast
    REBECCA SARA COOK; Fiscal Year: 2013
    ..However, many breast cancers with HER2 gene amplification do not respond and/or eventually escape trastuzumab and lapatinib...
  18. Alpha-synuclein degradation mechanisms
    Jianhua Zhang; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): a-synuclein (a-syn) mutations or gene amplification cause a small subset of Parkinson's disease (PD), with Lewy body (LB) formation, neurodegeneration and often an associated dementia...
  19. REPLICATION AND AMPLIFICATION OF TETRAHYMENA RDNA
    Geoffrey M Kapler; Fiscal Year: 2010
    ..rDNA replicon and provides a mechanism for selectively targeting ORC to the rDNA origin during programmed gene amplification. In this application, we propose experiments to determine the protein composition of this remarkable ORC ..
  20. Targeting the Urokinase Receptor in Glioblastoma Multiforme
    Steven L Gonias; Fiscal Year: 2013
    ..EGFR gene amplification is common in GBM and frequently accompanied by an in-frame deletion of exons 2-7, which yields a truncated ..
  21. c-Myb fusion proteins in Adenoid Cystic Carcinoma
    Timothy P Bender; Fiscal Year: 2012
    ..evidence has implicated c-Myb in human cancer until recent reports of chromosomal translocations and subtle gene amplification involving the MYB locus in several human cancers...
  22. GENE AMPLIFICATION BY A TRANSPOSITION APPARATUS
    Hiroshi Nakai; Fiscal Year: 2010
    ..This work will further define the cellular apparatus that maintains the stability and integrity of the genome, preventing genetic alterations associated with cellular dysfunction. ..
  23. Excitability and Synaptic Function of Cochlear Hair Cells
    Paul Fuchs; Fiscal Year: 2010
    ..Our ultimate aim will be to derive the contribution of VGCC gating to hair cell information transfer. ..
  24. Genome-wide map of Genetic Alteration in Human Pulmonary Hypertension Lungs
    Christopher D Coldren; Fiscal Year: 2010
    ..We and others have demonstrated that genetic alterations such as loss of heterozygosity (LOH), gene amplification or deletion, aneuploidy, and uniparental isodisomy can be efficiently characterized across the entire genome ..
  25. Validation and extension of an existing risk model for lung cancer
    Carol J Etzel; Fiscal Year: 2010
    ..chromosome breaks;nucleoplasmic bridges reflecting chromosome rearrangements and nuclear buds reflecting gene amplification) but also other cellular events (apoptosis and necrosis)...
  26. Structure of the Telomere Shelterin Complex
    Ming Lei; Fiscal Year: 2012
    ..Tumor karyotypes display three main types of alterations: loss of material, gene amplification, and chromosome rearrangement...
  27. A genetic engineering strategy for the improved production of the anti-helminthic
    JEFFREY DAVID KITTENDORF; Fiscal Year: 2012
    ..Rational genetic engineering strategies, such as gene deletion or gene amplification, will be applied to key genes in efforts to rationally generate a high producing mutant phenotype...
  28. FACTORS CONTROLLING TRANSCRIPTION AND CHROMATIN IN YEAST
    FRED M WINSTON; Fiscal Year: 2013
    ..Our previous work identified a previously unknown mechanism for histone gene amplification. By genetic and molecular approaches, we plan to understand the mechanism of this amplification and the gene ..
  29. Stat5 in Progression of Prostate Cancer
    Marja T Nevalainen; Fiscal Year: 2013
    ..2) Determine the diagnostic and functional significance of Stat5a/b gene amplification for prostate cancer progression to CR disease and clinical outcome...
  30. EphB4 Receptor Tyrosine Kinase RTK Targeted Humanized Monoclonal Antibody h131
    VALERY G KRASNOPEROV; Fiscal Year: 2012
    ..will be performed in addition to those already done to determine if Kras mutant tumors or tumors with EphB4 gene amplification are more susceptible to h131 treatment measured by tumor regression instead of reduction in the rate of ..
  31. The Role of OTX2 in Molecular Pathogenesis of Medulloblastoma
    Hai Yan; Fiscal Year: 2010
    ..to determine the oncogenic effects of OTX2 overexpression and to determine the extent and prevalence of OTX2 gene amplification;(2) to determine the effects of OTX2 inhibition on medulloblastoma cell survival and proliferation;and (3) ..
  32. Differential DNA Replication in Drosophila Development
    Terry L Orr-Weaver; Fiscal Year: 2013
    ..has been amplified and these are associated with tumor progression, but the primary mechanisms causing gene amplification are unknown...
  33. Lung Adenocarcinoma Invasion Genomics
    Charles A Powell; Fiscal Year: 2013
    ..the role of stromal influences on invasion, investigate the diagnostic and therapeutic implications of gene amplification, and to understand the mechanisms that repress invasion in AIS and promote invasion in adenocarcinoma...
  34. Tsg101 - a Modulator of ErbB2 Signaling in Breast Cancer
    Kay Uwe Wagner; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: A significant subset of invasive breast cancers exhibit Her2/neu gene amplification with an unfavorable prognosis...
  35. Breast Cancer Risk and Molecular Change After Chernobyl
    Scott Davis; Fiscal Year: 2012
    ..samples to assess breast cancer characteristics, including hormone receptor status, loss of heterozygosity, gene amplification, and epigenetic gene inactivation, and to estimate the association between these characteristics and ..
  36. Role of regulation of eukaryotic DNA replication in preserving genomic stability
    Joachim J Li; Fiscal Year: 2013
    ..More recently, we provided the first evidence that re-replication is a highly efficient means to induce gene amplification (Green et al, Science, in press)...
  37. Target Validation and Drug Development with Aptamers for Basal-like Breast Cancer
    HUA contact SHI; Fiscal Year: 2010
    ..The poor prognosis of BLBC patients is partly due to the lack of estrogen receptor expression and HER2 gene amplification, thus they are not treatable by biologically-based drugs...
  38. Identifying Mutations that Promote Microbial Evolvability
    JEFFREY EVAN BARRICK; Fiscal Year: 2013
    ..The third aim is to construct chromosomal reporters with selectable markers for measuring gene amplification and deletion rates...
  39. Structure and Function of the Hepatitis C Virus Genome
    PETER contact SARNOW; Fiscal Year: 2010
    ..This application will study two important HCV RNA-protein interactions that regulate HCV gene amplification. A highly-structured RNA element is located in the viral 5'noncoding region that functions as an ..
  40. Novel Gene Networks in Breast Development and Cancer
    Steffi Oesterreich; Fiscal Year: 2009
    ..and their potential as targets for treatment and prevention, and we will seek to integrate comprehensive gene amplification and expression information combining two molecular profiling approaches...
  41. ERBB2 TARGETED ANTITUMOR STRATEGIES IN BREAST CANCER
    Carlos L Arteaga; Fiscal Year: 2013
    ..In many cases, these alterations coexist with HER2 gene amplification and potentially mediate resistance to HER2 antagonists...
  42. DNA Mismatch Repair and associated genes in suppression of GI adenomas and carcin
    Steven M Lipkin; Fiscal Year: 2013
    ..In Aim 3 we will follow up in greater depth our discovery that TLE6-like gene amplification accelerates progression of MMR deficient GI tumors...
  43. VEGF Gene Amplification/Haplotype as Biomarkers for Bevacizumab in Breast Cancer
    BRYAN PAUL SCHNEIDER; Fiscal Year: 2013
    ..This proposal has the potential to unveil a predictive signature which will select a subgroup who should receive bevacizumab. ..
  44. Multi-Spectral Targeted Imaging for Early Detection of Cancer in Barrett's Esopha
    Thomas D Wang; Fiscal Year: 2013
    ..In Project 1, genomic data will be analyzed to identify molecular targets based on properties of gene amplification and/or overexpression...
  45. Heparanase Mechanisms in Brain-metastatic Breast Cancer
    Dario Marchetti; Fiscal Year: 2013
    ..we discovered the expression of heparanase in CTCs, and a significant correlation between its presence, EGFR gene amplification, and ALDH1, a known cancer stem cell marker...
  46. The Sixth International Mdm2 Workshop
    James J Manfredi; Fiscal Year: 2011
    ..such findings, Mdm2 has been implicated as also playing a role in human tumors with its overexpression or gene amplification being observed in a variety of cancers...
  47. DNA inverted repeats as an at-risk motif for palindromic gene amplification
    Hisashi Tanaka; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The goal of our research is to define the initiation mechanism of gene amplification in cancer cells...
  48. REPLICATION AND AMPLIFICATION OF TETRAHYMENA RDNA
    Geoffrey Kapler; Fiscal Year: 2000
    ..b>Gene amplification is frequently involved in tumorigenesis and, therefore, of significant medical importance...
  49. The Seventh International Mdm2 Workshop
    James J Manfredi; Fiscal Year: 2013
    ..such findings, Mdm2 has been implicated as also playing a role in human tumors with its overexpression or gene amplification being observed in a variety of cancers...
  50. HER2 regulation of luminal breast cancer stem cells
    Max S Wicha; Fiscal Year: 2013
    ..Although the use of HER2 targeting agents such as trastuzumab has been limited to breast cancers with HER2 gene amplification, recent retrospective analyses of adjuvant trastuzumab studies suggests that a much wider group of breast ..
  51. CrPV IRES function and animal virus replication in yeast
    SUNNIE THOMPSON; Fiscal Year: 2006
    ..of the picornaviral proteins, little is known about the host cell factors that are required for viral gene amplification. Identification of host cell factors has been hampered by the absence of an easily amenable genetic system...
  52. DRUG RESISTANCE AND GENE AMPLIFICATION IN LEISHMANIA
    Stephen Beverley; Fiscal Year: 2002
    b>Gene amplification and drug resistance is an important phenomenon in the biology and chemotherapy of Leishmania, as both laboratory and clinical isolates can often develop resistance to drugs in clinical usage (pentavalent antimonials) or ..
  53. CELLULAR PROCESSING OF DAMAGED DNA--ROLE IN ONCOGENESIS
    Philip Hanawalt; Fiscal Year: 2000
    ..to activation of protooncogenes or inactivation of tumor suppressor genes through mutation, recombination, gene amplification, translocation, or other chromosomal abnormalities...
  54. TAS::75 0893::TAS RAPID LARGE SCALE PRODUCTION OF PROTEIN THERAPEUTICS
    Wenda Gao; Fiscal Year: 2011
    ..of high producers, and uses the strongest signal sequence for high level secretory expression without gene amplification. This system shortens mamallina cell line development from 1 year to 4-5 weeks...
  55. PATHOBIOLOGY OF BREAST CANCER AND HORMONE RECEPTORS
    Michael Press; Fiscal Year: 2003
    ..related to study design, especially sample size, sensitivity and specificity of analytic methods used for gene amplification / overexpression and the potential confounding effect of differential treatment responsiveness, have been ..
  56. Characterizing Notch3 Signaling in Ovarian Cancer
    Tian Li Wang; Fiscal Year: 2013
    ..Based on our recent findings showing Notch3 gene amplification in ovarian cancers and its role in maintaining cell survival, we hypothesize that i) activation of Notch3 ..
  57. GENOMIC INSTABILITY IN TUMORS OF TRANSGENIC MICE
    Jon Mirsalis; Fiscal Year: 1999
    ..b>Gene amplification, microsatellite alterations, and chromosome aberrations have been observed in many tumor types...
  58. Transcription Coupled DNA Repair and Human Disease
    Philip Hanawalt; Fiscal Year: 2006
    ..to activation of proto-oncogenes or inactivation of tumor suppressor genes through mutation, recombination, gene amplification, translocation, or other chromosomal abnormalities...
  59. Role of Protein (S14)in Normal and Neoplastic Mammary
    WILLIAM KINLAW; Fiscal Year: 2005
    ..In addition to S14 gene amplification, we find S14 overexpression in the majority of tumors, as is the case for cyclin D1...
  60. Use of nanotechnology to rapidly detect human pathogens
    RICHARD MONTAGNA; Fiscal Year: 2005
    ..By eliminating enzymatic gene amplification steps, POC testing can be more easily accomplished within the rapid time frame expected for such tests...
  61. HER-2 NEU PROTO-ONCOGENE IN OVARIAN & ENDOMETRIAL CANCER
    Michael Press; Fiscal Year: 1993
    ..b>Gene amplification will be compared with messenger RNA levels, oncoprotein levels and tissue/cellular distribution of ..
  62. ELA COOPERATIVE ONCOGENE PRODUCTS IN HUMAN TUMOR CELLS
    JOHN RUPPERT; Fiscal Year: 1999
    DESCRIPTION: Identification of growth regulatory genes that are altered by base mutation, gene amplification, or rearrangement is a major focus of cancer research...
  63. X-IRRADIATION, DRUG RESISTANCE AND GENE AMPLIFICATION
    Peter Hahn; Fiscal Year: 1992
    ..clonal variability specifically with respect to the development of resistance to chemotherapeutic agents by gene amplification, and other mutations...
  64. Gene Amplification-Sciarid DNA Puffs
    SUSAN GERBI; Fiscal Year: 2006
    ..Information gained from the unique Sciara system should behelpful in understanding the mechanisms used by metazoa to specify an origin and to regulate its activation. ..
  65. Characterization of the Chromosome 17q23 Amplicon
    Fergus Couch; Fiscal Year: 2006
    DESCRIPTION: (provided by applicant) In cancer, gene amplification represents a type of genetic alteration that results in increased copy number of a gene or genes and subsequent increases in protein expression...
  66. IMMUNOLOGICAL CHARACTERIZATION OF CELLS
    Emmanuel Akporiaye; Fiscal Year: 1992
    ..clonal variability specifically with respect to the development of resistance to chemotherapeutic agents by gene amplification, and other mutations...