Browsing by Author "Rounbehler, Robert J."

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    Clinical and Genomic Features of Androgen Indifferent Prostate Cancer
    (MDPI, 2025-01-15) Masur, Jack; Ratan, Aakrosh; Wierbilowicz, Krzysztof; Ayanambakkam, Adanma; Churchman, Michelle L.; Graham, Laura S.; Grass, George Daniel; Gupta, Sumati; Kern, Sean Q.; King, Jennifer; Myint, Zin; Rounbehler, Robert J.; Salhia, Bodour; Singer, Eric A.; Zakharia, Yousef; Paschal, Bryce M.; Viscuse, Paul V.; Medicine, School of Medicine
    Androgen-indifferent prostate cancer (AIPC) is increasingly common and particularly lethal. Data describing these tumors are sparse, and AIPC remains a poorly understood malignancy. Utilizing the Oncology Research Information Exchange Network (ORIEN) database, we enriched for tumors with features of AIPC using previously described characteristics. Our AIPC cohort included three subgroups: aggressive variant prostate cancer (AVPC), neuroendocrine PC (NEPC), and double-negative PC (DNPC). Of 1496 total PC patients available for analysis, we identified 323 (22%) as MCRPC. Of those, 39 (12%) met AIPC criteria (17 AVPC, 13 NEPC, 9 DNPC) and 284 (88%) were non-AIPC. Forty-three percent of AIPC patients had de novo metastatic disease vs. 15% for non-AIPC (p = 0.003). Homologous recombination deficiency (HRD) and tumor mutational burden (TMB) did not differ between cohorts, but microsatellite instability scores (MSI) were significantly higher in AIPC (p = 0.019). Using Gene Set Enrichment Analysis (GSEA), we found that genes defining response to androgens and genes involved in oxidative phosphorylation were the most downregulated, whereas genes involved in epithelial-mesenchymal transition (EMT) and immune signaling were significantly upregulated in AIPC vs. non-AIPC. Our study demonstrates the potential for predefined criteria that aim to enrich for AIPC and suggests opportunities for therapeutic investigation.
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    Global multi-ancestry genetic study elucidates genes and biological pathways associated with thyroid cancer and benign thyroid diseases
    (medRxiv, 2025-05-16) White, Samantha L.; Brasher, Maizy S.; Pattee, Jack; Zhou, Wei; Chapman, Sinéad; Jee, Yon Ho; Bell, Caitlin C.; Jamil, Taylor L.; Barrio, Martin; Hirbo, Jibril; Cox, Nancy J.; Straub, Peter; Namba, Shinichi; Bertucci-Richter, Emily; Guare, Lindsay; EdrisMohammed, Ahmed; Morris, Sam; Mulford, Ashley J.; Zhang, Haoyu; Fennessy, Brian; Tobin, Martin D.; Chen, Jing; Williams, Alexander T.; John, Catherine; van Heel, David A.; Mathur, Rohini; Finer, Sarah; Moksnes, Marta Riise; Brumpton, Ben; Åsvold, Bjørn Olav; Peculis, Raitis; Rovite, Vita; Konrade, Ilze; Wang, Ying; Crooks, Kristy; Chavan, Sameer; Fisher, Matthew J.; Rafaels, Nicholas; Lin, Meng; Shortt, Jonathan; Sanders, Alan R.; Whiteman, David; MacGregor, Stuart; Medland, Sarah; Thorsteinsdóttir, Unnur; Stefánsson, Kári; Karaderi, Tugce; Egan, Kathleen M.; Bocklage, Therese; McCrary, Hilary C.; Riedlingeer, Greg; Salhia, Bodour; Shriver, Craig; Phan, Minh D.; Farlow, Janice L.; Edge, Stephen; Kaur, Varinder; Churchman, Michelle; Rounbehler, Robert J.; Brock, Pamela L.; Ringel, Matthew D.; Pividori, Milton; Schweppe, Rebecca; Raeburn, Christopher D.; Walters, Robin; Chen, Zhengming; Li, Liming; Matsuda, Koichi; Okada, Yukinori; Zoellner, Sebastian; Verma, Anurag; Preuss, Michael; Kenny, Eimear; Hendricks, Audrey; Fishbein, Lauren; Kraft, Peter; Daly, Mark; Neale, Benjamin; Biobank at the Colorado Center for Personalized Medicine; Genes & Health Research Team; BioBank Japan Project; Martin, Alicia; Cole, Joanne B.; Haugen, Bryan R.; Gignoux, Christopher R.; Pozdeyev, Nikita; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Thyroid diseases are common and highly heritable. Under the Global Biobank Meta-analysis Initiative, we performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer, benign nodular goiter, Graves' disease, lymphocytic thyroiditis, and primary hypothyroidism. We analyzed genetic association data from ~2.9 million genomes and identified 235 known and 501 novel independent variants significantly linked to thyroid diseases. We discovered genetic correlations between thyroid cancer, benign nodular goiter, and autoimmune thyroid diseases (r 2 =0.21-0.97). Telomere maintenance genes contribute to benign and malignant thyroid nodular disease risk, whereas cell cycle, DNA repair, and DNA damage response genes are predominantly associated with thyroid cancer. We proposed a paradigm explaining genetic predisposition to benign and malignant thyroid nodules. We evaluated thyroid cancer polygenic risk scores (PRS) for clinical applications in thyroid cancer diagnosis. We found PRS associations with thyroid cancer risk features: multifocality, lymph node metastases, and extranodal extension.