Hibbard M K, Kozakewich H P, Dal Cin P, Sciot R, Tan X, Xiao S, Fletcher J A
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Cancer Res. 2000 Sep 1;60(17):4869-72.
Lipoblastomas are pediatric neoplasms resulting from transformation of adipocytes. These benign tumors are typically composed of adipose cells in different stages of maturation within a variably myxoid matrix, and they contain clonal rearrangements of chromosome band 8q12. Because lipoblastomas resemble embryonic adipose tissue, characterization of their transforming mechanisms might reveal biological pathways in physiological adipogenesis. Herein, we demonstrate that lipoblastoma chromosome 8q12 rearrangements bring about promoter-swapping events in the PLAG1 oncqgene. We show that the hyaluronic acid synthase 2 (HAS2) or collagen 1 alpha 2 (COL1A2) gene promoter regions are fused to the entire PLAG1 coding sequence in each of four lipoblastomas. PLAG1 is a developmentally regulated zinc finger gene whose tumorigenic function has been shown previously only in epithelial salivary gland cells. Our findings reveal that PLAG1 activation, presumably resulting from transcriptional up-regulation, is a central oncogenic event in lipoblastoma.
脂肪母细胞瘤是由脂肪细胞转化形成的儿科肿瘤。这些良性肿瘤通常由处于不同成熟阶段的脂肪细胞组成，存在于可变的黏液样基质中，并且它们含有8号染色体q12带的克隆重排。由于脂肪母细胞瘤类似于胚胎脂肪组织，对其转化机制的表征可能揭示生理脂肪生成中的生物学途径。在此，我们证明脂肪母细胞瘤8号染色体q12重排在PLAG1癌基因中引发启动子交换事件。我们发现，在四个脂肪母细胞瘤中的每一个中，透明质酸合酶2（HAS2）或胶原蛋白1α2（COL1A2）基因启动子区域都与整个PLAG1编码序列融合。PLAG1是一个受发育调控的锌指基因，其致瘤功能此前仅在上皮唾液腺细胞中得到证实。我们的研究结果表明，PLAG1激活可能是由于转录上调，是脂肪母细胞瘤中的一个核心致癌事件。
