{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:18:50Z","timestamp":1788347930816,"version":"build-2803163510"},"reference-count":69,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T00:00:00Z","timestamp":1634428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000199","name":"United States Department of Agriculture","doi-asserted-by":"publisher","award":["2013-67015-21330"],"award-info":[{"award-number":["2013-67015-21330"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"United States Department of Agriculture","doi-asserted-by":"publisher","award":["2005-35205-16679"],"award-info":[{"award-number":["2005-35205-16679"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"United States Department of Agriculture","doi-asserted-by":"publisher","award":["CA-D*-ASC-7233-RR"],"award-info":[{"award-number":["CA-D*-ASC-7233-RR"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"United States Department of Agriculture","doi-asserted-by":"publisher","award":["CA-D*-ASC-6414-RR"],"award-info":[{"award-number":["CA-D*-ASC-6414-RR"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"United States Department of Agriculture","doi-asserted-by":"publisher","award":["CA-D*-ASC-7281-RR"],"award-info":[{"award-number":["CA-D*-ASC-7281-RR"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The avian \u03b1-herpesvirus known as Marek\u2019s disease virus (MDV) linearly integrates its genomic DNA into host telomeres during infection. The resulting disease, Marek\u2019s disease (MD), is characterized by virally-induced lymphomas with high mortality. The temporal dynamics of MDV-positive (MDV+) transformed cells and expansion of MD lymphomas remain targets for further understanding. It also remains to be determined whether specific host chromosomal sites of MDV telomere integration confer an advantage to MDV-transformed cells during tumorigenesis. We applied MDV-specific fluorescence in situ hybridization (MDV FISH) to investigate virus-host cytogenomic interactions within and among a total of 37 gonad lymphomas and neoplastic splenic samples in birds infected with virulent MDV. We also determined single-cell, chromosome-specific MDV integration profiles within and among transformed tissue samples, including multiple samples from the same bird. Most mitotically-dividing cells within neoplastic samples had the cytogenomic phenotype of \u2018MDV telomere-integrated only\u2019, and tissue-specific, temporal changes in phenotype frequencies were detected. Transformed cell populations composing gonad lymphomas exhibited significantly lower diversity, in terms of heterogeneity of MDV integration profiles, at the latest stages of tumorigenesis (&gt;50 days post-infection (dpi)). We further report high interindividual and lower intraindividual variation in MDV integration profiles of lymphoma cells. There was no evidence of integration hotspots into a specific host chromosome(s). Collectively, our data suggests that very few transformed MDV+ T cell populations present earlier in MDV-induced lymphomas (32\u201350 dpi), survive, and expand to become the dominant clonal population in more advanced MD lymphomas (51\u201362 dpi) and establish metastatic lymphomas.<\/jats:p>","DOI":"10.3390\/genes12101630","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T23:13:32Z","timestamp":1634512412000},"page":"1630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Marek\u2019s Disease Virus Telomeric Integration Profiles of Neoplastic Host Tissues Reveal Unbiased Chromosomal Selection and Loss of Cellular Diversity during Tumorigenesis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-0842","authenticated-orcid":false,"given":"Marla C.","family":"Glass","sequence":"first","affiliation":[{"name":"Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of California Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-4644","authenticated-orcid":false,"given":"Hans H.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Avian Disease and Oncology Laboratory, United States Department of Agriculture, Agricultural Research Service, East Lansing, MI 48823, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Delany","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of California Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nrmicro1382","article-title":"Marek\u2019s Disease Virus: From Miasma to Model","volume":"4","author":"Osterrieder","year":"2006","journal-title":"Nat. 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