文章：

X染色体遗传学与人类癌症

X-Chromosome Genetics and Human Cancer

原文发布日期：2004-08-01

DOI: 10.1038/nrc1413

类型: Review Article

开放获取: 否

要点：

1. Although female mammals carry two copies of the X chromosome, both male and female mammalian cells carry a single active X chromosome, as in females one copy of the X chromosome is inactivated.
2. Both of the main types of genetic alterations that lead to cancer — tumour-suppressor inactivation and oncogene activation — act dominantly when they affect the single active copy of an X-linked gene. The same alterations remain silent when they affect the inactivated X chromosome in female cells.
3. Increased dosage of X-linked genes is thought to represent a key event in oncogenesis. Two principal mechanisms that achieve such change in gene dosage are commonly observed in tumours: gain of whole copies or regions of the active X chromosome and loss or skewing of the inactivation mechanism.
4. As for autosomal genes, the expression of X-linked genes can be altered by changes in methylation, in addition to classic genetic mutations. Increases and decreases in methylation of X-chromosome genes have been implicated in certain cancers.
5. Some genes that are located on the inactive X chromosome escape inactivation in normal cells and several of these are implicated in human cancer.
6. Translocations involving regions of the X chromosome have unique outcomes in relation to ability to cause cancer. Events involving relocation of regions of the inactive X chromosome to an autosome can result in the reactivation of previously silent X-linked genes, with potential oncogenic effects. Conversely, loss of expression of an autosomal tumour suppressor can result from translocation to the inactive X chromosome.
7. Defects in the X-chromosome inactivation process can lead to cancer. The BRCA1 tumour suppressor is thought to have a key role in X-chromosome inactivation, and it has been proposed that loss of this function contributes to the development of cancer when normal expression of this gene is lost.

要点翻译：

1. 尽管雌性哺乳动物携带两条X染色体，但雌雄哺乳动物细胞中都只有一条活性X染色体，因为雌性细胞中的一条X染色体会失活。
2. 导致癌症的两类主要遗传变异——肿瘤抑制基因失活和癌基因激活——在影响X连锁基因的唯一活性拷贝时均呈现显性作用。而当这些变异影响雌性细胞中的失活X染色体时，它们将保持沉默。
3. X连锁基因剂量增加被认为是致癌过程中的关键事件。肿瘤中常见两种实现基因剂量改变的主要机制：获得活性X染色体的完整拷贝或区域，以及失活机制的缺失或偏斜。
4. 与常染色体基因类似，除经典基因突变外，X连锁基因的表达还可通过甲基化水平改变而发生变化。X染色体基因甲基化水平升高或降低与特定癌症的发生相关。
5. 部分位于失活X染色体上的基因在正常细胞中会逃脱失活，其中若干基因已被证实与人类癌症相关。
6. 涉及X染色体区域的易位在致癌能力方面具有独特表现：当失活X染色体区域易位至常染色体时，可能重新激活原本沉默的X连锁基因，产生潜在致癌效应；反之，常染色体肿瘤抑制基因若易位至失活X染色体则可能导致其表达缺失。
7. X染色体失活过程缺陷可诱发癌症。BRCA1肿瘤抑制基因被认为在X染色体失活中起关键作用，有研究提出当该基因正常表达缺失时，此项功能的丧失会促进癌症发展。

英文摘要：

In mammals, the X chromosome is unique within the chromosome set. In contrast to the other chromosomes — for which two active copies are present — both male and female cells carry only one active X chromosome. This is because males have only one X chromosome and in females only one copy is active, a situation that leads to specific characteristics for genes located on this chromosome. How are the outcomes of genetic events involved in cancer — namely activation of oncogenes and inactivation of tumour suppressors — expected to be different when these genes are carried on the X chromosome rather than on autosomes?

摘要翻译： 

在哺乳动物中，X染色体在整个染色体组中是独特的。与其他染色体不同——后者通常存在两个活跃拷贝——无论雄性还是雌性细胞，都仅携带一条活跃的X染色体。这是因为雄性只有一条X染色体，而雌性虽有两条X染色体，却也只有一条保持活性，这一状况导致位于该染色体上的基因具有特定特征。那么，当涉及癌症的遗传事件——即原癌基因的激活与抑癌基因的失活——其后果，在这些基因位于X染色体而非常染色体上时，预计会有何不同？

原文链接：

X-Chromosome Genetics and Human Cancer