In:
Microorganisms, MDPI AG, Vol. 10, No. 2 ( 2022-02-09), p. 401-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2076-2607
DOI:
10.3390/microorganisms10020401
Language:
English
Publisher:
MDPI AG
Publication Date:
2022
detail.hit.zdb_id:
2720891-6
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