Carbonara C, Longa L, Grosso E, Borrone C, Garrè M G, Brisigotti M, Migone N
CNR Centro Immunogenetica ed Oncologia Sperimentale, Università di Torino, italy.
Hum Mol Genet. 1994 Oct;3(10):1829-32. doi: 10.1093/hmg/3.10.1829.
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.
结节性硬化症是一种常染色体显性疾病，其特征是在多种器官和组织中形成多个错构瘤。目前已确定两个主要基因座：位于9号染色体q34的TSC1和位于16号染色体p13.3的TSC2。最近在一些结节性硬化症患者的错构瘤病变中观察到16p13.3相关标记的杂合性缺失。在此，我们报告了一例家族性结节性硬化症病例的巨细胞星形细胞瘤中TSC1关键区域杂合性缺失的首个证据。分离分析表明，丢失的9q34单倍型携带推定的正常TSC1基因。这些数据支持结节性硬化症错构瘤发生存在种系和体细胞功能丧失突变的假说，并提示TSC1基因产物也具有肿瘤抑制样活性。最后，讨论了在同一星形细胞瘤中发现的9p21第二个小杂合性缺失区域的可能意义。
