Genomic imprinting and environment in hereditary paraganglioma
Genomic imprinting and environment in hereditary paraganglioma
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DOI：
10.1002/ajmg.c.30018
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发表时间：
2004-08-15
影响因子：
3.1
通讯作者：
Baysal, BE
中科院分区：
文献类型：
--
作者：
Baysal, BE
遗传性副神经节瘤（PGL）的特征是副神经节系统中生长缓慢且血管化的肿瘤。PGL是由SDHB（PGL 4）、SDHC（PGL 3）或SDHD（PGL 1）基因中的种系杂合失活突变引起的，这些基因编码线粒体复合物II（琥珀酸脱氢酶; SDH）的四个亚基中的三个。常见的肿瘤部位包括颈部的颈动脉体和腹部的副神经节。与SDHD突变相关的肿瘤发展风险由传递父母的性别决定，因为只有父亲传递才会导致后代的肿瘤发生。这种传输模式表明SDHD基因上的基因组印记的操作。还有证据表明，在较高的海拔地区，SDHD突变携带者患肿瘤的风险增加。因此，荷兰SDHD突变的流行率增加，归因于多个创始人突变，部分原因是该国的低海拔，这可能会降低基因突变率并放松自然选择。因此，由SDHD突变引起的PGL代表了遗传性单基因肿瘤综合征的一个不寻常的例子，因为肿瘤发生的风险显示出对传递父母性别的绝对依赖性，并且可能被普遍存在的环境因素所改变。(C)2004 Wiley-Liss，Inc.
Hereditary paraganglioma (PGL) is characterized by the development of slow-growing and vascularized tumors in the paraganglionic system. PGL is caused by germ line heterozygous inactivating mutations in the SDHB (PGL4), SDHC (PGL3), or SDHD (PGL 1) genes, which encode three of the four subunits of mitochondrial complex II (succinate dehydrogenase; SDH). Common tumor sites include the carotid body in the neck and paraganglia in the abdomen. The risk of tumor development associated with SDHD mutations is determined by the sex of the transmitting parent, because only a paternal transmission leads to tumorigenesis in the progeny. This transmission pattern suggests operation of genomic imprinting on the SDHD gene. There is also evidence that the risk of tumor development increases at higher altitudes among SDHD mutation carriers. Accordingly, the increased prevalence of SDHD mutations in the Netherlands, attributable to multiple founder mutations, has been explained in part by the low altitudes in this country, which presumably reduce gene penetrance and relax the natural selection. Thus, PGL caused by SDHD mutations represents an unusual example of an inherited monogenic tumor syndrome because the risk of tumorigenesis shows an absolute dependence on the sex of the transmitting parent and may be modified by a ubiquitous environmental factor. (C) 2004 Wiley-Liss, Inc.