Tallini G, Vanni R, Manfioletti G, Kazmierczak B, Faa G, Pauwels P, Bullerdiek J, Giancotti V, Van Den Berghe H, Dal Cin P
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Lab Invest. 2000 Mar;80(3):359-69. doi: 10.1038/labinvest.3780040.
High-mobility group (HMG) proteins are nonhistone nuclear proteins that play an important role in the regulation of chromatin structure and function. HMGI-C and HMGI(Y) are members of the HMGI family of HMG proteins, and their expression in adult tissues generally correlates with malignant tumor phenotypes. However, HMGI-C and HMGI(Y) dysregulation as a result of specific rearrangements involving 12q15 and 6p21, the respective chromosomal sites in which the HMGI-C and HMGI(Y) genes are located, is also identified in a variety of common benign mesenchymal tumors, such as lipomas and uterine leiomyomata. The general prevalence of HMGI-C and HMGI(Y) protein expression and its correlation with chromosomal alterations in these benign tumors are unknown. We analyzed 95 human tumors (20 lipomas, 21 pulmonary chondroid hamartomas, 26 uterine leiomyomata, and 28 endometrial polyps) representing a selection of the benign lesions in which karyotypic alterations involving the chromosomal regions 12q15 and 6p21 are frequently detected. All cases were successfully karyotyped and some of them analyzed by fluorescent in situ hybridization with probes spanning the HMGI-C and HMGI(Y) genes. The results of this study demonstrate that expression of HMGI-C or HMGI(Y) is a common occurrence in lipomas, pulmonary chondroid hamartomas, leiomyomata, and endometrial polyps; that it correlates with 12q15 and 6p21 chromosomal alterations (p < 0.001); and that it is compatible with rearrangement of the HMGI-C and HMGI(Y) genes. The expression pattern and cellular localization of the immunoreactivity support the view that in biphasic lesions composed of a mixture of both stromal and epithelial cells, such as pulmonary chondroid hamartoma and endometrial polyps, the mesenchymal component is the site of the HMGI genetic alterations.
高迁移率族（HMG）蛋白是非组蛋白核蛋白，在染色质结构和功能的调节中起重要作用。HMGI-C和HMGI(Y)是HMG蛋白HMGI家族的成员，它们在成体组织中的表达通常与恶性肿瘤表型相关。然而，在多种常见的良性间叶组织肿瘤中，如脂肪瘤和子宫平滑肌瘤，也发现了由于涉及12q15和6p21（分别为HMGI-C和HMGI(Y)基因所在的染色体位点）的特定重排导致的HMGI-C和HMGI(Y)失调。这些良性肿瘤中HMGI-C和HMGI(Y)蛋白表达的总体发生率及其与染色体改变的相关性尚不清楚。我们分析了95例人类肿瘤（20例脂肪瘤、21例肺软骨瘤、26例子宫平滑肌瘤和28例子宫内膜息肉），这些肿瘤代表了一组经常检测到涉及染色体区域12q15和6p21的核型改变的良性病变。所有病例均成功进行了核型分析，其中一些病例用跨越HMGI-C和HMGI(Y)基因的探针进行了荧光原位杂交分析。本研究结果表明，HMGI-C或HMGI(Y)的表达在脂肪瘤、肺软骨瘤、平滑肌瘤和子宫内膜息肉中很常见；它与12q15和6p21染色体改变相关（p<0.001）；并且与HMGI-C和HMGI(Y)基因的重排一致。免疫反应性的表达模式和细胞定位支持这样一种观点，即在由基质细胞和上皮细胞混合组成的双相性病变中，如肺软骨瘤和子宫内膜息肉，间叶成分是HMGI基因改变的部位。
