9Q34 LOSS OF HETEROZYGOSITY IN A TUBEROUS SCLEROSIS ASTROCYTOMA SUGGESTS A GROWTH SUPPRESSOR-LIKE ACTIVITY ALSO FOR THE TSC1 GENE
9Q34 LOSS OF HETEROZYGOSITY IN A TUBEROUS SCLEROSIS ASTROCYTOMA SUGGESTS A GROWTH SUPPRESSOR-LIKE ACTIVITY ALSO FOR THE TSC1 GENE
复制标题
DOI：
10.1093/hmg/3.10.1829
复制
发表时间：
1994-10-01
影响因子：
3.5
通讯作者：
MIGONE, N
中科院分区：
文献类型：
--
作者：
CARBONARA, C;LONGA, L;MIGONE, N
结节性硬化症是一种常染色体显性遗传病，其特征是在各种器官和组织中发展成多发性错构瘤。到目前为止，已经确定了两个主要的基因座：位于染色体9q34上的TSC1和位于染色体16p13.3的TSC2。最近在一些结节性硬化症患者的错构瘤皮损中观察到16p13.3相关标记物的杂合性丢失。在这里，我们报告了家族性结节性硬化症巨细胞星形细胞瘤中TSC1关键区域杂合性缺失的第一个证据。分离分析表明，丢失的9q34单倍型携带假定正常的TSC1基因。这些数据支持了生殖系和躯体功能丧失突变导致结节性硬化症错构瘤发生的假说，并表明TSC1基因产物也具有肿瘤抑制活性。最后，讨论了在同一星形细胞瘤中发现的在9p21的第二个小杂合性缺失区域的可能意义。
Tuberous sclerosis is an autosomal dominant disease whose characteristic feature is the development of multiple hamartomas in a variety of organs and tissues. Two major loci have been identified so far: TSC1 on chromosome 9q34 and TSC2 on chromosome 16p13.3. Loss of heterozygosity at 16p13.3-associated markers has been recently observed in hamartomatous lesions of some tuberous sclerosis patients. Here we report the first evidence of loss of heterozygosity at the TSC1 critical region in a giant cell astrocytoma of a familial tuberous sclerosis case. Segregation analysis showed that the 9q34 haplotype lost carried the putative normal TSC1 gene. These data support the hypothesis of both a germline and somatic loss-of-function mutation for the development of tuberous sclerosis hamartomas and suggest a tumor-suppressor-like activity also for the TSC1 gene product. Finally, the possible significance of a second small region of loss of heterozygosity at 9p21, found in the same astrocytoma, is discussed.