Recent progress in microarray technology has been related to the development of high resolution microarrays which can map genomic alterations and constitutional variants in DNA copy number at an extremely high resolution. We have applied high resolution arrays in this fashion to several systems and have also adapted this technology to the mapping of DNase I hypersensitive sites. Recently, we have demonstrated that they can be used to map DNA origins of replication. We have also worked to push the limits of detection by extending sample types to formalin fixed, paraffin embedded samples, flow sorted primary cells and fine needle aspirates. We have established that useful nucleic acid preparations can be obtained from these fixed tissues and are continuing to extend the analysis of this material for a wider range of genomic technologies. Current efforts have been directed primarily at the implementation of next generation sequencing technologies. These methods primarily depend on producing an array of DNA molecules which are sequentially imaged during the sequencing reaction. We are investigating the use of these methods for gene expression profiling for large and small RNAs, for the detection of genome rearrangements, mutations, and for the measurement of chromatin modifications, DNase I hypersensitive sites, and transcription factor localization. A major part of this effort is the development of a powerful computational environment which can be used to analyze the massive amount of sequence data which is generated by this work. Although this is a challenging process, it ultimately will yield a streamlined analysis pipeline in which multiple sequence based assays will be easy to integrate and free of array platform specific artifacts. Specific goals of our computational efforts include the optimization of pipelines to process sequence data for chromatin analysis, chromosome rearrangements, gene expression, and mutation detection. We are currently engaged in pursuing new approaches to target sequencing efforts to the small proportion of the genome composed of genes in order to be able to sequence thousands of genes in individual samples and in a complementary fashion, to sequence a few key genes in hundreds of samples. These are goals are being accomplished with the aid of thousands of synthetic oligonucleotides which are used to target the desired portion of the genome.

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National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Zhu, Xuguang; Enomoto, Keisuke; Zhao, Li et al. (2017) Bromodomain and Extraterminal Protein Inhibitor JQ1 Suppresses Thyroid Tumor Growth in a Mouse Model. Clin Cancer Res 23:430-440
Goldberg, Liat; Gough, Sheryl M; Lee, Fan et al. (2017) Somatic mutations in murine models of leukemia and lymphoma: Disease specificity and clinical relevance. Genes Chromosomes Cancer 56:472-483
Yang, Youfeng; Vocke, Cathy D; Ricketts, Christopher J et al. (2017) Genomic and metabolic characterization of a chromophobe renal cell carcinoma cell line model (UOK276). Genes Chromosomes Cancer 56:719-729
Enomoto, Keisuke; Zhu, Xuguang; Park, Sunmi et al. (2017) Targeting MYC as a Therapeutic Intervention for Anaplastic Thyroid Cancer. J Clin Endocrinol Metab 102:2268-2280
Si, H; Lu, H; Yang, X et al. (2016) TNF-? modulates genome-wide redistribution of ?Np63?/TAp73 and NF-?B cREL interactive binding on TP53 and AP-1 motifs to promote an oncogenic gene program in squamous cancer. Oncogene 35:5781-5794
Yang, Baiyu; Shebl, Fatma M; Sternberg, Lawrence R et al. (2016) Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the United States. PLoS One 11:e0166828
Saxena, Neetu; Maio, Nunziata; Crooks, Daniel R et al. (2016) SDHB-Deficient Cancers: The Role of Mutations That Impair Iron Sulfur Cluster Delivery. J Natl Cancer Inst 108:
Neychev, V; Sadowski, S M; Zhu, J et al. (2016) Neuroendocrine Tumor of the Pancreas as a Manifestation of Cowden Syndrome: A Case Report. J Clin Endocrinol Metab 101:353-8
Li, Jun; Woods, Susan L; Healey, Sue et al. (2016) Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant. Am J Hum Genet 98:830-842
Killian, J Keith; Dorssers, Lambert C J; Trabert, Britton et al. (2016) Imprints and DPPA3 are bypassed during pluripotency- and differentiation-coupled methylation reprogramming in testicular germ cell tumors. Genome Res 26:1490-1504

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