) The long term goals of Core A, Molecular and Cellular Assays, are [1] to provide genotypic and phenotypic characterization of WRN wild-type, heterozygous, and null human- and mouse-derived cells, cell lines, or tissues generated by this program, and [2] to procure and bank sarcomas and meningiomas for the Program Project in order to perform WRN sequence analysis. These goals will be achieved by the following specific aims: 1. In human cell lines in which WRN expression has been manipulated by allele transfer; in cells and cell lines derived from tissues of knock out mice; and in yeast the Core will provide: a. analysis of genomic instability by cytogenetic examination for gross chromosomal rearrangements characteristic of Werner's syndrome, including whole chromosome loss or gain and variegated translocation mosaicism. b. assessment of WRN expression at the RNA level. c. DNA sequence analysis for verification of WRN gene mutations. 2. For sarcomas and meningiomas obtained from surgical resections, the Core will collect and bank tissue for histologic characterization and DNA and RNA isolation for use in the Program Project and perform WRN DNA sequence analysis of paired normal and tumor samples.
| Orozco, Javier I J; Knijnenburg, Theo A; Manughian-Peter, Ayla O et al. (2018) Epigenetic profiling for the molecular classification of metastatic brain tumors. Nat Commun 9:4627 |
| Schmitt, Michael W; Pritchard, Justin R; Leighow, Scott M et al. (2018) Single-Molecule Sequencing Reveals Patterns of Preexisting Drug Resistance That Suggest Treatment Strategies in Philadelphia-Positive Leukemias. Clin Cancer Res 24:5321-5334 |
| Mikheev, Andrei M; Mikheeva, Svetlana A; Severs, Liza J et al. (2018) Targeting TWIST1 through loss of function inhibits tumorigenicity of human glioblastoma. Mol Oncol 12:1188-1202 |
| Lee, Su-In; Celik, Safiye; Logsdon, Benjamin A et al. (2018) A machine learning approach to integrate big data for precision medicine in acute myeloid leukemia. Nat Commun 9:42 |
| Salk, Jesse J; Schmitt, Michael W; Loeb, Lawrence A (2018) Enhancing the accuracy of next-generation sequencing for detecting rare and subclonal mutations. Nat Rev Genet 19:269-285 |
| Davis, Luther; Zhang, Yinbo; Maizels, Nancy (2018) Assaying Repair at DNA Nicks. Methods Enzymol 601:71-89 |
| Yu, Ming; Heinzerling, Tai J; Grady, William M (2018) DNA Methylation Analysis Using Droplet Digital PCR. Methods Mol Biol 1768:363-383 |
| Knijnenburg, Theo A; Wang, Linghua; Zimmermann, Michael T et al. (2018) Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas. Cell Rep 23:239-254.e6 |
| Kamath-Loeb, Ashwini S; Zavala-van Rankin, Diego G; Flores-Morales, Jeny et al. (2017) Homozygosity for the WRN Helicase-Inactivating Variant, R834C, does not confer a Werner syndrome clinical phenotype. Sci Rep 7:44081 |
| Oshima, Junko; Sidorova, Julia M; Monnat Jr, Raymond J (2017) Werner syndrome: Clinical features, pathogenesis and potential therapeutic interventions. Ageing Res Rev 33:105-114 |
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