Oncotarget

Research Papers:

Integration of ALV into CTDSPL and CTDSPL2 genes in B-cell lymphomas promotes cell immortalization, migration and survival

Shelby Winans, Alyssa Flynn, Sanandan Malhotra, Vidya Balagopal and Karen L. Beemon _

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Oncotarget. 2017; 8:57302-57315. https://doi.org/10.18632/oncotarget.19328

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Abstract

Shelby Winans1, Alyssa Flynn1, Sanandan Malhotra1, Vidya Balagopal1 and Karen L. Beemon1

1Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA

Correspondence to:

Karen L. Beemon, email: [email protected]

Keywords: CTD small phosphatase like proteins, ALV, lymphoma, immortalization, migration

Received: April 28, 2017     Accepted: June 09, 2017     Published: July 18, 2017

ABSTRACT

Avian leukosis virus induces tumors in chickens by integrating into the genome and altering expression of nearby genes. Thus, ALV can be used as an insertional mutagenesis tool to identify novel genes involved in tumorigenesis. Deep sequencing analysis of viral integration sites has identified CTDSPL and CTDSPL2 as common integration sites in ALV-induced B-cell lymphomas, suggesting a potential role in driving oncogenesis. We show that in tumors with integrations in these genes, the viral promoter is driving the expression of a truncated fusion transcript. Overexpression in cultured chick embryo fibroblasts reveals that CTDSPL and CTDSPL2 have oncogenic properties, including promoting cell migration. We also show that CTDSPL2 has a previously uncharacterized role in protecting cells from apoptosis induced by oxidative stress. Further, the truncated viral fusion transcripts of both CTDSPL and CTDSPL2 promote immortalization in primary cell culture.


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