{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:16:11Z","timestamp":1777608971293,"version":"3.51.4"},"reference-count":72,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["2013-67015-21330"],"award-info":[{"award-number":["2013-67015-21330"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Marek\u2019s disease virus (MDV) is the causative agent for Marek\u2019s disease (MD), which is characterized by T-cell lymphomas in chickens. While the viral Meq oncogene is necessary for transformation, it is insufficient, as not every bird infected with virulent MDV goes on to develop a gross tumor. Thus, we postulated that the chicken genome contains cancer driver genes; i.e., ones with somatic mutations that promote tumors, as is the case for most human cancers. To test this hypothesis, MD tumors and matching control tissues were sequenced. Using a custom bioinformatics pipeline, 9 of the 22 tumors analyzed contained one or more somatic mutation in Ikaros (IKFZ1), a transcription factor that acts as the master regulator of lymphocyte development. The mutations found were in key Zn-finger DNA-binding domains that also commonly occur in human cancers such as B-cell acute lymphoblastic leukemia (B-ALL). To validate that IKFZ1 was a cancer driver gene, recombinant MDVs that expressed either wild-type or a mutated Ikaros allele were used to infect chickens. As predicted, birds infected with MDV expressing the mutant Ikaros allele had high tumor incidences (~90%), while there were only a few minute tumors (~12%) produced in birds infected with the virus expressing wild-type Ikaros. Thus, in addition to Meq, key somatic mutations in Ikaros or other potential cancer driver genes in the chicken genome are necessary for MDV to induce lymphomas.<\/jats:p>","DOI":"10.3390\/microorganisms10020401","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T21:22:15Z","timestamp":1644441735000},"page":"401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification and Validation of Ikaros (IKZF1) as a Cancer Driver Gene for Marek\u2019s Disease Virus-Induced Lymphomas"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-1047","authenticated-orcid":false,"given":"Alec","family":"Steep","sequence":"first","affiliation":[{"name":"Genetics Program, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evin","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Avian Disease and Oncology Laboratory, US National Poultry Research Center, Agricultural Research Service, USDA, East Lansing, MI 48823, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongen","family":"Xu","sequence":"additional","affiliation":[{"name":"Genome-Oriented Bioinformatics, Technical University of Munich, D-80333 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cari","family":"Hearn","sequence":"additional","affiliation":[{"name":"Avian Disease and Oncology Laboratory, US National Poultry Research Center, Agricultural Research Service, USDA, East Lansing, MI 48823, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitrij","family":"Frishman","sequence":"additional","affiliation":[{"name":"Genome-Oriented Bioinformatics, Technical University of Munich, D-80333 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Niikura","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V5A 1S6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7287-0916","authenticated-orcid":false,"given":"John R.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Endemic Poultry Viral Diseases Research, US National Poultry Research Center, Agricultural Research Service, USDA, Athens, GA 30605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5699-998X","authenticated-orcid":false,"given":"Taejoong","family":"Kim","sequence":"additional","affiliation":[{"name":"Endemic Poultry Viral Diseases Research, US National Poultry Research Center, Agricultural Research Service, USDA, Athens, GA 30605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven J.","family":"Conrad","sequence":"additional","affiliation":[{"name":"Endemic Poultry Viral Diseases Research, US National Poultry Research Center, Agricultural Research Service, USDA, Athens, GA 30605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William M.","family":"Muir","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA"},{"name":"Genesys Bioinformatics Service, Punta Gorda, FL 33950, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, US National Poultry Research Center, Agricultural Research Service, USDA, East Lansing, MI 48823, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"ref_1","unstructured":"OECD\/FAO (2021). 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