The zinc finger SET domain gene Prdm14 is overexpressed in lymphoblastic lymphomas with retroviral insertions at Evi32.
BACKGROUND
AKXD recombinant inbred strains of mice have proven to be very useful in the identification of potential oncogenes and tumor suppressors involved in the development of lymphoid and myeloid malignancies. In these tumors, the hematopoietic insertion of an active AKV murine leukemia virus (MuLV) is associated with the onset of disease. Common sites of retroviral insertion (CIS) identify genes causally associated with the development or initiation of lymphoma.


METHODS
In the present study, we analyzed a previously uncharacterized CIS, Ecotropic Viral Integration Site 32 (Evi32), which is located on mouse chromosome 1. We analyzed candidate genes in the region to identify those involved in Evi32 mediated oncogenesis.


RESULTS
Here we show that proviral insertion at Evi32 correlates with significant overexpression of a putative transcription factor, PR-domain containing 14 (Prdm14). Tumors with insertions at Evi32 are consistently lymphoid in nature. Prdm14 is normally expressed early in embryonic development with the highest expression in undifferentiated embryonic stem (ES) cells. This study implicates Prdm14 as a proto-oncogene involved in lymphoblastic lymphoma formation.
Dettman
E J
EJ
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
Justice
Monica J
MJ
D000818:Animals; D002875:Chromosomes; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051379:Mice; D016254:Mutagenesis, Insertional; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000235:genetics* / Q000821:virology; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D016601:RNA-Binding Proteins; D012190:Retroviridae / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D016662:Virus Integration; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; C531066:Prdm14 protein, mouse; D000090063:Proto-Oncogene Mas; D016601:RNA-Binding Proteins; D014157:Transcription Factors