Green A J, Johnson P H, Yates J R
Department of Clinical Genetics, Addenbrooke's NHS Trust, Cambridge, UK.
Hum Mol Genet. 1994 Oct;3(10):1833-4. doi: 10.1093/hmg/3.10.1833.
We have previously demonstrated allele loss in hamartomas from patients with tuberous sclerosis for markers spanning the tuberous sclerosis gene on chromosome 16q13.3 (TSC2). Germline deletions in the TSC2 gene have been shown in 5% of patients with tuberous sclerosis (TSC). These data support our hypothesis that the TSC2 gene acts as a growth suppressor gene, analogous to the traditional tumour suppressor gene. We now report a TSC hamartoma showing allele loss for markers on chromosome 9q34 in the region of the TSC1 gene. We studied six hamartomas from four sporadic and two familial cases of TSC, none of which showed allele loss for markers on chromosome 16p13.3. The hamartomas were paraffin embedded sections of three renal angiomyolipomas, two giant cell astrocytomas, and a cardiac rhabdomyoma. Eight markers were analysed, comprising from centromeric to telomeric ASS-D9S64-D9S149-ABO-D9S150-DBH-D9S66-D9S67++ +. One angiomyolipoma showed allele loss for the markers ABO, DBH and D9S66, but not for D9S149 or D9S67. The patient was not informative for D9S150. The family structure did not permit the phase of the disease and marker alleles to be determined. These finding support the hypothesis that the TSC1 gene on 9q34, like the TSC2 gene, acts as a growth suppressor. The data would place the TSC1 gene between D9S149 and D9S67. Mapping of allele loss in hamartomas may help in the refinement of the location of the TSC1 locus.
我们之前已经证明，对于位于16号染色体13.3区（TSC2）的结节性硬化症基因上的标记物，结节性硬化症患者错构瘤中存在等位基因缺失。在5%的结节性硬化症（TSC）患者中已发现TSC2基因的种系缺失。这些数据支持了我们的假设，即TSC2基因作为一种生长抑制基因，类似于传统的肿瘤抑制基因。我们现在报告一例TSC错构瘤，其在TSC1基因所在区域的9号染色体34区的标记物上显示等位基因缺失。我们研究了来自4例散发性和2例家族性TSC病例的6个错构瘤，其中没有一个在16号染色体13.3区的标记物上显示等位基因缺失。这些错构瘤是3个肾血管平滑肌脂肪瘤、2个巨细胞星形细胞瘤和1个心脏横纹肌瘤的石蜡包埋切片。分析了8个标记物，包括从着丝粒到端粒的ASS-D9S64-D9S149-ABO-D9S150-DBH-D9S66-D9S67++ +。一个肾血管平滑肌脂肪瘤在ABO、DBH和D9S66标记物上显示等位基因缺失，但在D9S149或D9S67上未显示。该患者对于D9S150无信息。家族结构不允许确定疾病和标记物等位基因的相位。这些发现支持了9号染色体34区的TSC1基因与TSC2基因一样作为生长抑制基因的假设。这些数据将把TSC1基因定位在D9S149和D9S67之间。错构瘤中等位基因缺失的定位可能有助于精确定位TSC1基因座。
