PLAG1 fusion oncogenes in lipoblastoma

Lipoblastomas are pediatric neoplasms resulting from transformation of adip ocytes. These benign tumors are typically composed of adipose cells in diff erent stages of maturation within a variably myxoid matrix, and they contai n clonal rearrangements of chromosome band 8q12, Because lipoblastomas rese mble embryonic adipose tissue, characterization of their transforming mecha nisms might reveal biological pathways in physiological adipogenesis, Herei n, we demonstrate that lipoblastoma chromosome 8q12 rearrangements bring ab out promoter-swapping events in the PLAG1 oncogene, We show that the hyalur onic acid synthase 2 (HAS2) or collagen 1 alpha 2 (COL1A2) gene promoter re gions are fused to the entire PLAG1 coding sequence in each of four lipobla stomas. PLAG1 is a developmentally regulated zinc finger gene whose tumorig enic function has been shown previously only in epithelial salivary gland c ells. Our findings reveal that PLAG1 activation, presumably resulting from transcriptional up-regulation, Is a central oncogenic event in lipoblastoma .