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

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 <i>CTDSPL</i> and <i>CTDSPL2</i> 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 <i>CTDSPL</i> and <i>CTDSPL2</i> have oncogenic properties, including promoting cell migration. We also show that <i>CTDSPL2</i> has a previously uncharacterized role in protecting cells from apoptosis induced by oxidative stress. Further, the truncated viral fusion transcripts of both <i>CTDSPL</i> and <i>CTDSPL2</i> promote immortalization in primary cell culture.