Clonality of tuberous sclerosis harmatomas shown by non-random X-chromosome inactivation
Clonality of tuberous sclerosis harmatomas shown by non-random X-chromosome inactivation
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DOI：
10.1007/bf02265273
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发表时间：
1996-02-01
期刊：
影响因子：
5.3
通讯作者：
Yates, JRW
中科院分区：
文献类型：
--
作者：
Green, AJ;Sepp, T;Yates, JRW
脑硬化症（TSC）是一种常染色体显性疾病，其特征是脑和其他器官中的肿瘤样畸形（错构瘤）。一部分错构瘤患者TSC表现出DNA标记的杂合性缺失（洛），该DNA标记位于染色体9 q34上的TSC 1基因或16p13.3上的TSC 2基因区域。这意味着这些病变是克隆性的。我们研究了X染色体失活。作为克隆性的标志，在13个错构瘤与TSC的女性。错构瘤包括五个肾血管平滑肌脂肪瘤，三个纤维瘤和七个其他病变。在以前的研究中，有4个病变显示洛缺失。采用聚合酶链反应分析Xq 11 -12上雄激素受体三联重复多态性相邻的HpaII限制性位点的差异甲基化。在12个病变中，有一个倾斜的失活模式，一个X染色体完全甲基化，另一个未甲基化。正常组织表现出随机的失活模式。这些数据证实，大多数TSC错构瘤是克隆起源。这是一个有趣的发现，因为这些病变由一种以上的细胞类型组成。
Tuberous sclerosis (TSC) is an autosomal dominant condition characterised by tumour-like malformations (hamartomas) in the brain and other organs. A proportion of hamartomas from patients with TSC show loss of heterozygosity (LOH) for DNA markers in the region of either the TSC1 gene on chromosome 9q34 or the TSC2 gene on 16p13.3. This implies that these lesions are clonal. We have studied X-chromosome inactivation. as a marker of clonality, in 13 hamartomas from females with TSC. The hamartomas comprised five renal angiomyolipomas, three fibromas and seven other lesions. In previous studies, four of the lesions showed LOH. A polymerase chain reaction assay was used to analyse differential methylation of an HpaII restriction site adjacent to the androgen-receptor triplet-repeat polymorphism on Xq11-12. In 12 of the lesions, there was a skewed inactivation pattern with one X chromosome being fully methylated and the other unmethylated. Normal tissue showed a random pattern of inactivation. These data confirm that most TSC hamartomas are clonal in origin. This is an intriguing finding, since these lesions are composed of more than one cell type.