HMGIC, the gene for an architectural transcription factor, is amplified and rearranged in a subset of human sarcomas
HMGIC, the gene for an architectural transcription factor, is amplified and rearranged in a subset of human sarcomas
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DOI：
10.1038/sj.onc.1201135
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发表时间：
1997-06-19
期刊：
影响因子：
8
通讯作者：
Myklebost, O
中科院分区：
文献类型：
--
作者：
Berner, JM;MezaZepeda, LA;Myklebost, O
12号染色体长臂的扩增片段在人类肉瘤中经常被观察到，在大多数情况下，在MDM 2和CDK 4基因周围存在单独的扩增区域，在这里，我们显示了包含HMGIC的第三个区域的反复扩增，HMGIC是一种人类建筑转录因子基因，观察到基因侧翼序列的扩增频率降低，表明在扩增子中包含该第三区域也是选择的，在三个样品中仅HMGIC的5 ′部分被扩增，表明在扩增之前或期间基因的3 ′部分优先丢失，在其他几个样品中观察到基因重排，表达分析显示转录物大小异常，缺乏3'序列，一个样品的3' RACE显示外显子4和5被异位序列取代，HMGIC的这种截短类似于良性肿瘤（包括脂肪瘤）中HMGIC易位的报道，并且令人惊讶的是，该基因在网状分化的脂肪肉瘤（脂肪瘤的恶性对应物）中频繁扩增或重排，似乎可以想象，高水平的全长或截短的hmgic可能与这些肿瘤的病因有关。
Amplified segments of the long arm of chromosome 12 are frequently observed in human sarcomas, In most cases there are separate amplified regions around the MDM2 and CDK4 genes, Here we show recurrent amplification of a third region encompassing HMGIC, a human architectural transcription factor gene, Reduced amplification frequency of sequences flanking the gene was observed, indicating that inclusion of this third region in the amplicons is also selected for, In three samples only the 5' part of HMGIC was amplified, suggesting preferential loss of the 3' part of the gene preceding or during amplification, In several other samples rearrangement of the gene was observed, Expression analysis showed transcripts of aberrant sizes, lacking 3' sequences, and 3' RACE of one sample revealed replacement of exons 4 and 5 with ectopic sequences, This truncation of HMGIC resembles that reported for translocations of HMGIC in benign tumors, including Lipomas, and it is striking that the gene was frequently amplified or rearranged in web differentiated Liposarcomas, the malignant counterpart of lipomas, It seems conceivable that high levels of either full length or truncated hmgic could be relevant for the etiology of these tumors.