Browsing by Author "Spellman, Paul"

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    Integrated analysis of genome-wide DNA methylation and gene expression profiles in molecular subtypes of breast cancer
    (Oxford University Press, 2013) Rhee, Je-Keun; Kim, Kwangsoo; Chae, Heejoon; Evans, Jared; Yan, Pearlly; Zhang, Byoung-Tak; Gray, Joe; Spellman, Paul; Huang, Tim H. M.; Nephew, Kenneth P.; Kim, Sun; Cellular and Integrative Physiology, School of Medicine
    Aberrant DNA methylation of CpG islands, CpG island shores and first exons is known to play a key role in the altered gene expression patterns in all human cancers. To date, a systematic study on the effect of DNA methylation on gene expression using high resolution data has not been reported. In this study, we conducted an integrated analysis of MethylCap-sequencing data and Affymetrix gene expression microarray data for 30 breast cancer cell lines representing different breast tumor phenotypes. As well-developed methods for the integrated analysis do not currently exist, we created a series of four different analysis methods. On the computational side, our goal is to develop methylome data analysis protocols for the integrated analysis of DNA methylation and gene expression data on the genome scale. On the cancer biology side, we present comprehensive genome-wide methylome analysis results for differentially methylated regions and their potential effect on gene expression in 30 breast cancer cell lines representing three molecular phenotypes, luminal, basal A and basal B. Our integrated analysis demonstrates that methylation status of different genomic regions may play a key role in establishing transcriptional patterns in molecular subtypes of human breast cancer.
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    The Integrated Genomic Landscape of Thymic Epithelial Tumors
    (Elsevier, 2018-02) Radovich, Milan; Pickering, Curtis R.; Felau, Ina; Ha, Gavin; Zhang, Hailei; Jo, Heejoon; Hoadley, Katherine A.; Anur, Pavana; Zhang, Jiexin; McLellan, Mike; Bowlby, Reanne; Matthew, Thomas; Danilova, Ludmila; Hegde, Apurva M.; Kim, Jaegil; Leiserson, Mark D. M.; Sethi, Geetika; Lu, Charles; Ryan, Michael; Su, Xiaoping; Cherniack, Andrew D.; Robertson, Gordon; Akbani, Rehan; Spellman, Paul; Weinstein, John N.; Hayes, D. Neil; Raphael, Ben; Lichtenberg, Tara; Leraas, Kristen; Zenklusen, Jean Claude; Pathology and Laboratory Medicine, School of Medicine
    Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy.