Liao Dezhong Joshua, Du Qian-qian, Yu Bennett W, Grignon David, Sarkar Fazlul H
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
Cancer Invest. 2003;21(4):641-58. doi: 10.1081/cnv-120022385.
In an XX female, one of the two X chromosomes has been inactivated during early embryonic life to achieve a compensation of X-linked gene products between males and females, leaving only one allele of X-linked genes functional. There are some X-linked genes escaping the X-inactivation, i.e., being expressed from both alleles. Escape from X-inactivation varies at different levels; some genes have both alleles active in some women but only one allele active in others, whereas some other genes have both alleles active in neoplastic tissue but only one allele active normally. The X-inactivation may be considered functionally equivalent to a loss of heterozygosity (LOH) for some genes, whereas escape from X-inactivation may be equivalent to functional gene amplification for others. The physiological LOH may make X-linked tumor suppressor genes lose their function more easily, compared with autosomal tumor suppressor genes, thus predisposing women to cancer formation more easily. Moreover, the human X chromosome contains many genes related to cancer or to sex and reproduction. All these properties of the X chromosome suggest that it may play more important roles than any autosomal chromosome in the development and progression of reproductive and urologic cancers.
在一名XX女性中，两条X染色体中的一条在胚胎早期就已失活，以实现男性和女性之间X连锁基因产物的补偿，使得X连锁基因只有一个等位基因具有功能。存在一些逃避X染色体失活的X连锁基因，即从两个等位基因都表达。逃避X染色体失活在不同水平上存在差异；一些基因在一些女性中两个等位基因都活跃，但在另一些女性中只有一个等位基因活跃，而另一些基因在肿瘤组织中两个等位基因都活跃，但正常情况下只有一个等位基因活跃。对于某些基因而言，X染色体失活在功能上可能等同于杂合性缺失（LOH），而逃避X染色体失活对于其他基因可能等同于功能性基因扩增。与常染色体肿瘤抑制基因相比，生理性杂合性缺失可能使X连锁肿瘤抑制基因更容易丧失其功能，从而使女性更容易患癌。此外，人类X染色体包含许多与癌症或性别及生殖相关的基因。X染色体的所有这些特性表明，它在生殖和泌尿系统癌症的发生和发展中可能比任何常染色体发挥更重要的作用。
