Finelli Palma, Pierantoni Giovanna Maria, Giardino Daniela, Losa Marco, Rodeschini Ornella, Fedele Monica, Valtorta Emanuele, Mortini Pietro, Croce Carlo M, Larizza Lidia, Fusco Alfredo
Laboratory of Medical Cytogenetics and Molecular Genetics, Istituto Auxologico Italiano, Via Viotti 3/4, 20123 Milan, Italy.
Cancer Res. 2002 Apr 15;62(8):2398-405.
Trisomy of chromosome 12 is a nonrandom chromosomal change in pituitary adenomas, particularly prolactinomas. This and the finding that prolactin-secreting pituitary adenomas develop in transgenic mice overexpressing the wild-type HMGA2 gene (which maps to 12q14-15) prompted us to investigate HMGA2 rearrangements and expression in human prolactinomas. By dual-color interphase fluorescence in situ hybridization analysis using HMGA2-specific PACs and BACs, we found that the HMGA2 locus was amplified in seven of the eight prolactinoma samples examined. The cytogenetic manifestations of elevated HMGA2 concentrations ranged from simple trisomy to tetrasomy 12 and der(12) chromosomes to marker chromosomes bearing 12q14-15-derived regions. Reverse transcription-PCR, Western blot and immunohistochemical analysis showed HMGA2 overexpression in a number of prolactinomas bearing rearrangement of regions 12q14-15. These data suggest a critical role of the HMGA2 overexpression in the generation of prolactin-secreting pituitary adenomas in humans.
12号染色体三体是垂体腺瘤，尤其是催乳素瘤中一种非随机的染色体改变。这一现象以及在过表达野生型HMGA2基因（定位于12q14 - 15）的转基因小鼠中出现分泌催乳素的垂体腺瘤这一发现，促使我们研究HMGA2在人催乳素瘤中的重排和表达情况。通过使用HMGA2特异性的PACS和BAC进行双色间期荧光原位杂交分析，我们发现在所检测的8个催乳素瘤样本中有7个样本的HMGA2基因座发生了扩增。HMGA2浓度升高的细胞遗传学表现从单纯三体到12号染色体四体、der(12)染色体，再到携带12q14 - 15衍生区域的标记染色体不等。逆转录 - PCR、蛋白质免疫印迹和免疫组化分析显示，在一些存在12q14 - 15区域重排的催乳素瘤中HMGA2过表达。这些数据表明HMGA2过表达在人类分泌催乳素的垂体腺瘤的发生过程中起关键作用。
