| Autor: |
Alec Steep, Evin Hildebrandt, Hongen Xu, Cari Hearn, Dmitrij Frishman, Masahiro Niikura, John R. Dunn, Taejoong Kim, Steven J. Conrad, William M. Muir, Hans H. Cheng |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Microorganisms, Vol 10, Iss 2, p 401 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2076-2607 |
| DOI: |
10.3390/microorganisms10020401 |
| Popis: |
Marek’s disease virus (MDV) is the causative agent for Marek’s 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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