{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNote that none of the provided abstracts discuss SNORD66. Instead, they all focus on SNF5 (also known as SMARCB1 or INI1), a core subunit of the SWI/SNF chromatin remodeling complex that functions as a potent tumor suppressor. SNF5 plays a key role in orchestrating epigenetic programs by modulating chromatin structure and gene transcription. It antagonizes oncogenic factors such as EZH2, regulates stem cell–associated transcriptional programs, and governs cell cycle progression; its loss leads to aberrant H3K27 trimethylation, misregulation of differentiation-associated genes, and activation of oncogenic pathways that contribute to aggressive tumor formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in transcriptional regulation, SNF5 is essential for maintaining proper nucleosome positioning and chromatin architecture. Perturbations in its activity disrupt the balance of key signaling pathways—including Hedgehog, p53-dependent DNA damage responses, and pathways governing cell metabolism and differentiation—which in turn can lead to genomic instability and tumorigenesis. Conditional inactivation studies in primary cells and various mouse models demonstrate that loss of SNF5 function not only impairs cell survival and differentiation (with effects seen, for example, in the liver, central nervous system, and renal medulla) but also sensitizes cells to additional genetic insults, thereby accelerating malignant transformation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, genetically engineered mouse models reveal that SNF5 loss cooperates with other genetic alterations (such as p53 inactivation or reliance on residual components like BRG1) to promote a spectrum of tumors—including rhabdoid tumors, T-cell lymphomas, and other aggressive malignancies. These studies highlight that restoring proper chromatin remodeling function or targeting downstream oncogenic signaling (e.g., through inhibitors of pathways activated by SNF5 loss) may provide promising therapeutic avenues in SNF5‐deficient cancers. Overall, the wide-ranging influence of SNF5 on chromatin dynamics, transcriptional fidelity, and cell cycle control underscores its essential role in both normal development and tumor suppression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Boris G Wilson, Xi Wang, Xiaohua Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2010.09.006"}], "href": "https://doi.org/10.1016/j.ccr.2010.09.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20951942"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20951942"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Charles W M Roberts, Monique M Leroux, Mark D Fleming, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1535-6108(02)00185-x"}], "href": "https://doi.org/10.1016/s1535-6108(02"}, {"type": "t", "text": "00185-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12450796"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12450796"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zainab Jagani, E Lorena Mora-Blanco, Courtney G Sansam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.2251"}], "href": "https://doi.org/10.1038/nm.2251"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21076395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21076395"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Michael S Isakoff, Courtney G Sansam, Pablo Tamayo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0509014102"}], "href": "https://doi.org/10.1073/pnas.0509014102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16301525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16301525"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Michael Y Tolstorukov, Courtney G Sansam, Ping Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Swi/Snf chromatin remodeling/tumor suppressor complex establishes nucleosome occupancy at target promoters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1302209110"}], "href": "https://doi.org/10.1073/pnas.1302209110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23723349"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23723349"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xi Wang, Courtney G Sansam, Christopher S Thom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogenesis caused by loss of the SNF5 tumor suppressor is dependent on activity of BRG1, the ATPase of the SWI/SNF chromatin remodeling complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-09-0733"}], "href": "https://doi.org/10.1158/0008-5472.CAN-09-0733"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19789351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19789351"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Agnes Klochendler-Yeivin, Eli Picarsky, Moshe Yaniv "}, {"type": "b", "children": [{"type": "t", "text": "Increased DNA damage sensitivity and apoptosis in cells lacking the Snf5/Ini1 subunit of the SWI/SNF chromatin remodeling complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.26.7.2661-2674.2006"}], "href": "https://doi.org/10.1128/MCB.26.7.2661-2674.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16537910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16537910"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Elizabeth S McKenna, Courtney G Sansam, Yoon-Jae Cho, et al. 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