其他的分子生物学研究

垂体瘤的细胞遗传学分析表明核型的异常，主要涉及到1、4、7和19号染色体，对25例垂体腺瘤的分析发现，染色体获得性增加常见于X、7、8和5号染色体，而染色体丢失常见于11、9和13号染色体，染色体的结构异常较为少见，染色体的丢失和结构异常与肿瘤的生物学行为有一定关系。在散发的分泌生长激素的垂体瘤中发现了11q13部位的异常，11号染色体的11q13区域与Ⅰ型多发性内分泌肿瘤（multiple endocrine neoplasm，MEN）的发生有关，这种肿瘤综合征可涉及垂体、甲状旁腺和胰腺等腺体。10q，11q13和13q部位的杂合性缺失与垂体腺瘤的侵袭性有关，9p部位的缺失和p16基因的甲基化可能在垂体腺瘤发生的早期事件。p53、CREB、GHRH、nm23、p16和p27等基因状态和表达的改变参与了垂体腺瘤发病的多步骤的过程。Boggild等应用PCR技术对88例患者的垂体瘤研究中发现，36%的肿瘤存在Gsα的激活显性突变，对16例的肿瘤研究发现18%的肿瘤存在11号染色体的缺失，这种缺失主要发生在GH腺瘤、催乳素瘤、ACTH腺瘤和非功能腺瘤。其他的常染色体缺失的频率少于6%。在对2例侵袭性腺瘤的研究中发现了多处的常染色体缺失，这提示这种肿瘤的发展可能是一个多步骤渐进的过程，有趣的是，他们没有发现几种常见的癌基因的扩增和重排，包括N-ras、Myc、H-ras和fos。

最近的研究表明，肿瘤抑制基因MEN1的突变和印记（imprinting）在散发的垂体瘤的病理发生中不起决定作用，但在这类肿瘤的亚组中可能发挥重要作用。

垂体瘤中偶尔发现的遗传不稳定性，包括常染色体的缺失，提示这种肿瘤的发生是一个渐进的、多步骤的过程。但与其他肿瘤相比，垂体瘤的病理进程又有很大的不同，例如结肠癌的多步骤进展伴随多个基因的异常，病情的后期必然导致肿瘤转移，但人类垂体瘤的转移却极为罕见，垂体瘤和其他内分泌肿瘤抑制肿瘤转移的确切分子机制目前还不清楚。

在过去的几年里垂体瘤的分子生物学研究获得了飞快的进展，相信随着研究技术的进步，在未来的研究中将会获得越来越多的垂体瘤的分子生物学知识，会进一步增进我们对这种疾病的认识。将来的研究需明确相应的分子生物学的改变是否能够预测后来的垂体腺瘤的肿瘤行为和指导临床治疗。

（杨立业　惠国桢）

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