scholarly journals Selection for avian leukosis virus integration sites determines the clonal progression of B-cell lymphomas

2017 ◽  
Vol 13 (11) ◽  
pp. e1006708 ◽  
Author(s):  
Sanandan Malhotra ◽  
Shelby Winans ◽  
Gary Lam ◽  
James Justice ◽  
Robin Morgan ◽  
...  
Keyword(s):  
B Cell ◽  
Avian Leukosis Virus ◽  
B Cell Lymphomas ◽  
Integration Sites ◽  
Selection For ◽  
Virus Integration ◽  
Clonal Progression

scholarly journals Common Viral Integration Sites Identified in Avian Leukosis Virus-Induced B-Cell Lymphomas

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
James F. Justice ◽  
Robin W. Morgan ◽  
Karen L. Beemon
Keyword(s):  
B Cell ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Consensus Sequence ◽  
B Cell Lymphoma ◽  
Avian Leukosis Virus ◽  
B Cell Lymphomas ◽  
Genome Wide ◽  
Integration Sites

ABSTRACTAvian leukosis virus (ALV) induces B-cell lymphoma and other neoplasms in chickens by integrating within or near cancer genes and perturbing their expression. Four genes—MYC,MYB,Mir-155, andTERT—have previously been identified as common integration sites in these virus-induced lymphomas and are thought to play a causal role in tumorigenesis. In this study, we employ high-throughput sequencing to identify additional genes driving tumorigenesis in ALV-induced B-cell lymphomas. In addition to the four genes implicated previously, we identify other genes as common integration sites, includingTNFRSF1A,MEF2C,CTDSPL,TAB2,RUNX1,MLL5,CXorf57, andBACH2. We also analyze the genome-wide ALV integration landscapein vivoand find increased frequency of ALV integration near transcriptional start sites and within transcripts. Previous work has shown ALV prefers a weak consensus sequence for integration in cultured human cells. We confirm this consensus sequence for ALV integrationin vivoin the chicken genome.IMPORTANCEAvian leukosis virus induces B-cell lymphomas in chickens. Earlier studies showed that ALV can induce tumors through insertional mutagenesis, and several genes have been implicated in the development of these tumors. In this study, we use high-throughput sequencing to reveal the genome-wide ALV integration landscape in ALV-induced B-cell lymphomas. We find elevated levels of ALV integration near transcription start sites and use common integration site analysis to greatly expand the number of genes implicated in the development of these tumors. Interestingly, we identify several genes targeted by viral insertions that have not been previously shown to be involved in cancer.

scholarly journals Absence of missense mutations in activated c-myc genes in avian leukosis virus-induced B-cell lymphomas.

1988 ◽  
Vol 8 (6) ◽  
pp. 2659-2663 ◽  
Author(s):  
M Hahn ◽  
W S Hayward
Keyword(s):  
B Cell ◽  
Gene Product ◽  
Primary Structure ◽  
Avian Leukosis Virus ◽  
Nucleotide Sequences ◽  
Missense Mutations ◽  
B Cell Lymphomas ◽  
Altered Expression

We have determined the nucleotide sequences of two independent DNA clones which contained the activated c-myc genes from avian leukosis virus-induced B-cell lymphomas. Neither of these c-myc genes contained missense mutations. This strongly supports the notion that the c-myc proto-oncogene in avian leukosis virus-induced B-cell lymphomas can be oncogenically activated by altered expression of the gene without a change in the primary structure of the gene product.

Multiple proto-oncogene activations in avian leukosis virus-induced lymphomas: evidence for stage-specific events

1989 ◽  
Vol 9 (6) ◽  
pp. 2657-2664 ◽  
Author(s):  
B E Clurman ◽  
W S Hayward
Keyword(s):  
B Cell ◽  
Tumor Progression ◽  
Avian Leukosis Virus ◽  
Viral Integration ◽  
B Cell Lymphomas ◽  
Late Stages

We have examined avian leukosis virus-induced B-cell lymphomas for multiple, stage-specific oncogene activations. Three targets for viral integration were identified: c-myb, c-myc, and a newly identified locus termed c-bic. The c-myb and c-myc genes were associated with different lymphoma phenotypes. The c-bic locus was a target for integration in one class of lymphomas, usually in conjunction with c-myc activation. The data indicate that c-myc and c-bic may act synergistically during lymphomagenesis and that c-bic is involved in late stages of tumor progression.

scholarly journals Avian Leukosis Virus Activation of an Antisense RNA Upstream ofTERTin B-Cell Lymphomas

2016 ◽  
Vol 90 (20) ◽  
pp. 9509-9517 ◽  
Author(s):  
Jiri Nehyba ◽  
Sanandan Malhotra ◽  
Shelby Winans ◽  
Thomas H. O'Hare ◽  
James Justice ◽  
...  
Keyword(s):  
B Cell ◽  
Antisense Rna ◽  
Promoter Region ◽  
Gene Promoter ◽  
B Cell Lymphoma ◽  
Avian Leukosis Virus ◽  
Sequencing Analysis ◽  
Integration Sites ◽  
Viral Sequences ◽  
Deep Sequencing Analysis

ABSTRACTAvian leukosis virus (ALV) induces tumors by integrating its proviral DNA into the chicken genome and altering the expression of nearby genes via strong promoter and enhancer elements. Viral integration sites that contribute to oncogenesis are selected in tumor cells. Deep-sequencing analysis of B-cell lymphoma DNA confirmed that the telomerase reverse transcriptase (TERT) gene promoter is a common ALV integration target. Twenty-six unique proviral integration sites were mapped between 46 and 3,552 nucleotides (nt) upstream of theTERTtranscription start site, predominantly in the opposite transcriptional orientation toTERT. Transcriptome-sequencing (RNA-seq) analysis of normal bursa revealed a transcribed region upstream ofTERTin the opposite orientation, suggesting theTERTpromoter is bidirectional. This transcript appears to be an uncharacterized antisense RNA. We have previously shown thatTERTexpression is upregulated in tumors with integrations in theTERTpromoter region. We now report that the viral promoter drives the expression of a chimeric transcript containing viral sequences spliced to exons 4 through 7 of this antisense RNA. Clonal expansion of cells with ALV integrations driving overexpression of theTERTantisense RNA suggest it may have a role in tumorigenesis.IMPORTANCEThe data suggest that ALV integrations in the TERT promoter region drive the overexpression of a novel antisense RNA and contribute to the development of lymphomas.

Absence of missense mutations in activated c-myc genes in avian leukosis virus-induced B-cell lymphomas

1988 ◽  
Vol 8 (6) ◽  
pp. 2659-2663
Author(s):  
M Hahn ◽  
W S Hayward
Keyword(s):  
B Cell ◽  
Gene Product ◽  
Primary Structure ◽  
Avian Leukosis Virus ◽  
Nucleotide Sequences ◽  
Missense Mutations ◽  
B Cell Lymphomas ◽  
Altered Expression

We have determined the nucleotide sequences of two independent DNA clones which contained the activated c-myc genes from avian leukosis virus-induced B-cell lymphomas. Neither of these c-myc genes contained missense mutations. This strongly supports the notion that the c-myc proto-oncogene in avian leukosis virus-induced B-cell lymphomas can be oncogenically activated by altered expression of the gene without a change in the primary structure of the gene product.

scholarly journals Multiple proto-oncogene activations in avian leukosis virus-induced lymphomas: evidence for stage-specific events.

1989 ◽  
Vol 9 (6) ◽  
pp. 2657-2664 ◽  
Author(s):  
B E Clurman ◽  
W S Hayward
Keyword(s):  
B Cell ◽  
Tumor Progression ◽  
Avian Leukosis Virus ◽  
Viral Integration ◽  
B Cell Lymphomas ◽  
Late Stages

We have examined avian leukosis virus-induced B-cell lymphomas for multiple, stage-specific oncogene activations. Three targets for viral integration were identified: c-myb, c-myc, and a newly identified locus termed c-bic. The c-myb and c-myc genes were associated with different lymphoma phenotypes. The c-bic locus was a target for integration in one class of lymphomas, usually in conjunction with c-myc activation. The data indicate that c-myc and c-bic may act synergistically during lymphomagenesis and that c-bic is involved in late stages of tumor progression.

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