Browsing by Author "Brown, Noah"

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    Cutaneous Syncytial Myoepithelioma: A Recently Described Neoplasm Which May Mimic Nevoid Melanoma and Epithelioid Sarcoma
    (Wiley, 2017) Alomari, Ahmed K.; Brown, Noah; Andea, Aleodor; Betz, Bryan L.; Patel, Rajiv M.; Department of Pathology and Laboratory Medicine, School of Medicine
    Cutaneous syncytial myoepithelioma is a recently described rare tumor of the dermis. It is derived and composed purely of myoepithelial cells and shows a characteristic syncytial growth pattern of neoplastic cells with little intervening stroma and no recognizable ductal structures. It represents a diagnostic challenge to dermatopathologists given its rarity and unusual immunophenotype. Molecular testing for rearrangement of the EWSR1 gene plays a significant role in confirming the diagnosis in most cases. Herein, we present 2 cases with mundane clinical presentations and challenging histopathological findings. In both cases, the lesion was composed of relatively well-circumscribed proliferation of epithelioid and spindle cells in the superficial dermis growing in a syncytial fashion and showing focal adipocytic metaplasia. The 2 cases had slightly different immunohistochemical profiles, but shared focal positivity for S100, EMA and pan-keratin or p63. Break-apart FISH demonstrated the presence of an EWSR1 gene rearrangement confirming the diagnosis in both cases. We discuss the most important differential diagnoses, particularly melanocytic lesions and epithelioid sarcoma and the original diagnostic considerations that the cases were referred to us with. We also review the molecular features and spectrum of immunohistochemical findings in these lesions and their role in excluding entities in the differential diagnosis.
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    Replication stress increases de novo CNVs across the malaria parasite genome
    (bioRxiv, 2024-12-31) Brown, Noah; Luniewski, Aleksander; Yu, Xuanxuan; Warthan, Michelle; Liu, Shiwei; Zulawinska, Julia; Ahmad, Syed; Congdon, Molly; Santos, Webster; Xiao, Feifei; Guler, Jennifer L.; Radiology and Imaging Sciences, School of Medicine
    Changes in the copy number of large genomic regions, termed copy number variations (CNVs), contribute to important phenotypes in many organisms. CNVs are readily identified using conventional approaches when present in a large fraction of the cell population. However, CNVs that are present in only a few genomes across a population are often overlooked but important; if beneficial under specific conditions, a de novo CNV that arises in a single genome can expand during selection to create a larger population of cells with novel characteristics. While the reach of single cell methods to study de novo CNVs is increasing, we continue to lack information about CNV dynamics in rapidly evolving microbial populations. Here, we investigated de novo CNVs in the genome of the Plasmodium parasite that causes human malaria. The highly AT-rich P. falciparum genome readily accumulates CNVs that facilitate rapid adaptation to new drugs and host environments. We employed a low-input genomics approach optimized for this unique genome as well as specialized computational tools to evaluate the de novo CNV rate both before and after the application of stress. We observed a significant increase in genomewide de novo CNVs following treatment with a replication inhibitor. These stress-induced de novo CNVs encompassed genes that contribute to various cellular pathways and tended to be altered in clinical parasite genomes. This snapshot of CNV dynamics emphasizes the connection between replication stress, DNA repair, and CNV generation in this important microbial pathogen.