THE RETINOBLASTOMA GENE IS INVOLVED IN MALIGNANT PROGRESSION OF ASTROCYTOMAS
THE RETINOBLASTOMA GENE IS INVOLVED IN MALIGNANT PROGRESSION OF ASTROCYTOMAS
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DOI：
10.1002/ana.410360505
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发表时间：
1994-11-01
影响因子：
11.2
通讯作者：
LOUIS, DN
中科院分区：
文献类型：
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作者：
HENSON, JW;SCHNITKER, BL;LOUIS, DN
高达50%的人类星形细胞瘤发生13号染色体q缺失，表明该染色体上存在星形细胞瘤肿瘤抑制基因。为了确定13 q14上的视网膜母细胞瘤易感基因（Rb）是否有助于星形细胞瘤的形成，我们检查了85个肿瘤基因内Rb1.20位点的杂合性缺失（洛合性缺失）。洛缺失在54例高级别星形细胞瘤中检出16例（30%），而在12例低级别胶质瘤中未检出。13 q侧翼市场的缺失图谱显示Rb 1.20区域优先被缺失所靶向。用单链构象多态性（SSCP）分析和直接DNA测序检测Rb 1.20位点洛缺失的肿瘤中剩余Rb等位基因的突变。在外显子8（1个肿瘤）、外显子24（2个肿瘤）和内含子24（1个肿瘤）中检测到突变。免疫组化检测发现，9例洛中3例Rb蛋白表达改变，1例无洛的肿瘤Rb蛋白表达改变。我们的研究结果表明，Rb失活有助于形成高级别星形细胞瘤，因此牵连第二个，已知的肿瘤抑制基因在星形细胞瘤肿瘤发生。
Loss of chromosome 13q occurs in up to 50% of human astrocytomas, suggesting the presence of an astrocytoma tumor suppressor gene on that chromosome. To determine whether the retinoblastoma susceptibility gene (Rb) on 13q14 contributes to the formation of astrocytomas, we examined 85 tumors for loss of heterozygosity (LOH) at the intragenic Rb 1.20 locus. LOH was detected in 16 of 54 informative high-grade astrocytomas (30%), but was not detected in 12 low-grade gliomas. Deletion mapping with flanking markets on 13q revealed that the Rb 1.20 region was preferentially targeted by the deletions. Tumors with LOH at Rb 1.20 were examined for mutations in the remaining Rb allele using single-strand conformational polymorphism (SSCP) analysis and direct DNA sequencing. Mutations were detected in exon 8 (1 tumor), exon 24 (2 tumors), and intron 24 (1 tumor). Rb protein expression, as assessed by immunohistochemistry, was altered in 3 of 9 cases with LOH and in 1 tumor without LOH. Our results demonstrate that Rb inactivation contributes to the formation of high-grade astrocytomas, and therefore implicate a second, known tumor suppressor gene in astrocytoma tumorigenesis.