Röpke A, Kalinski T, Kluba U, von Falkenhausen U, Wieacker P F, Röpke M
Institute of Human Genetics, Otto-von-Guericke University Magdeburg, Germany.
Cytogenet Genome Res. 2007;119(1-2):33-8. doi: 10.1159/000109616. Epub 2007 Dec 14.
Lipoblastoma is a benign uncommon soft-tissue-tumor resembling fetal adipose tissue affecting mainly children under three years of age. In lipoblastoma, the typical cytogenetic changes are clonal rearrangements involving chromosomal region 8q11-->q13. The oncogene PLAG1 (pleomorphic adenoma gene 1) is located within this chromosomal region on band 8q12. Recent reports have demonstrated that in lipoblastoma, the PLAG1 gene is activated by 'promoter-swapping'. Herein, we demonstrate that in lipoblastoma, the PLAG1 gene may also be activated by low-level amplification. We report on a lipoblastoma with the karyotype 48 approximately 50,XX,del(8)(q13q21.2),+del(8)(q13q21.2)x4[cp12]. Subsequent FISH analysis on uncultured tumor cells confirmed this result and demonstrated a low-level amplification of the chromosomal region 8pter-->8q13 and 8q21.2-->8qter. A partial monosomy was seen for the chromosomal region 8q13-->8q21.2. No other gains or losses were observed by CGH analysis. RT-PCR analysis showed that the PLAG1 gene is activated in the tumor sample of the lipoblastoma analyzed, in contrast to normal fatty tissue without PLAG1 expression. In conclusion, our results demonstrate that low-level amplification is a further mechanism of PLAG1 activation in lipoblastomas.
脂肪母细胞瘤是一种罕见的良性软组织肿瘤，类似于胎儿脂肪组织，主要影响三岁以下儿童。在脂肪母细胞瘤中，典型的细胞遗传学改变是涉及染色体区域8q11→q13的克隆重排。癌基因PLAG1（多形性腺瘤基因1）位于8q12带的这个染色体区域内。最近的报告表明，在脂肪母细胞瘤中，PLAG1基因通过“启动子交换”被激活。在此，我们证明在脂肪母细胞瘤中，PLAG1基因也可能通过低水平扩增被激活。我们报告了一例核型为48,XX,del(8)(q13q21.2),+del(8)(q13q21.2)x4[cp12]的脂肪母细胞瘤。随后对未培养的肿瘤细胞进行的荧光原位杂交（FISH）分析证实了这一结果，并显示染色体区域8pter→8q13和8q21.2→8qter存在低水平扩增。在染色体区域8q13→8q21.2可见部分单体性。通过比较基因组杂交（CGH）分析未观察到其他的增加或缺失。逆转录-聚合酶链反应（RT-PCR）分析表明，与无PLAG1表达的正常脂肪组织相比，在分析的脂肪母细胞瘤肿瘤样本中PLAG1基因被激活。总之，我们的结果表明低水平扩增是脂肪母细胞瘤中PLAG1激活的另一种机制。
