Kazmierczak B, Dal Cin P, Wanschura S, Borrmann L, Fusco A, Van den Berghe H, Bullerdiek J
Center for Human Genetics and Genetic Counseling, University of Bremen, Germany.
Genes Chromosomes Cancer. 1998 Dec;23(4):279-85.
Specific chromosomal abnormalities of chromosomal region 6p21.3 have been described in subsets of many benign mesenchymal tumors. In the presented study, we investigated a series of 36 such cases by FISH, and Southern blot analyses for HMGIY rearrangements. FISH results revealed that the chromosomal breakpoints of 11 pulmonary chondroid hamartomas (PCHs), 12 endometrial polyps (EPs), one lipoma, and two uterine leiomyomas (ULs) were located within a 80 kb region surrounding the HMGIY gene. In 11 PCHs and one UL the breakpoints were located 3' of HMGIY, and one PCH showed a breakpoint 5' of HMGIY. Southern blot analyses with intra- and extragenic probes were performed of primary tumor material or cell lines from one UL, three PCHs, and five EPs. In none of these cases was an intragenic rearrangement found. Finally, we were able to detect expression of truncated HMGIY transcripts by 3'-RACE PCR. Our data clearly show the role of a further member of the HMGI family in the development of benign mesenchymal tumors. Although most of the breakpoints of the chromosomal translocations involving HMGIY are located outside the gene, aberrant transcripts resembling the structure of those observed in the case of HMGIC have been found. Our molecular investigations thus led to the identification of the molecular mechanism by which rearrangements of either of two closely related genes lead to the development of frequent benign mesenchymal tumors in humans.
许多良性间叶组织肿瘤亚群中已发现6号染色体p21.3区域存在特定的染色体异常。在本研究中，我们通过荧光原位杂交（FISH）以及针对HMGIY重排的Southern印迹分析，对36例此类病例进行了研究。FISH结果显示，11例肺软骨样错构瘤（PCH）、12例子宫内膜息肉（EP）、1例脂肪瘤和2例子宫平滑肌瘤（UL）的染色体断点位于HMGIY基因周围80 kb的区域内。在11例PCH和1例UL中，断点位于HMGIY基因的3'端，1例PCH的断点位于HMGIY基因的5'端。我们对1例UL、3例PCH和5例EP的原发性肿瘤组织或细胞系进行了基因内和基因外探针的Southern印迹分析。在这些病例中均未发现基因内重排。最后，我们通过3'-RACE PCR检测到了截短的HMGIY转录本的表达。我们的数据清楚地表明了HMGI家族的另一个成员在良性间叶组织肿瘤发生中的作用。虽然涉及HMGIY的染色体易位的大多数断点位于基因外，但已发现了与HMGIC病例中观察到的转录本结构相似的异常转录本。因此，我们的分子研究确定了两种密切相关基因中的任何一种重排导致人类常见良性间叶组织肿瘤发生的分子机制。
