CLONING AND ANALYSIS OF A NOVEL TUMOR SUPPRESSOR GENE

描述：研究人员已经确定了染色体3q的一个亚区 发生肿瘤特异性组成性杂合性缺失（洛）， 骨肉瘤发生过程中的高频率。 洛通常 与肿瘤抑制基因的存在有关， 洛。 Brachmann-DeLange综合征也是一种骨畸形综合征， 这一区域表明，肿瘤抑制基因和基因座， 畸形综合征可能是同一个基因 因此，这一具体目标 建议：1）从D3 S1212-D3 S1246中分离候选cDNA 2）鉴定候选cDNA的表达模式 与骨肉瘤肿瘤抑制基因活性一致; 3）进行 在骨肉瘤肿瘤中对那些候选cDNA进行突变分析， 表达模式与骨肉瘤肿瘤抑制基因一致 活性; 4）进行遗传突变的突变分析， 家族性骨肉瘤和Brachmann-DeLange综合征患者。

DESCRIPTION: The investigators have identified a subregion of chromosome 3q that undergoes tumor-specific loss of constitutional heterozygosity (LoH) at high frequency during osteosarcoma tumorigenesis. LoH is frequently associated with the presence of tumor suppressor gene within the region of LoH. A bone dysmorphology syndrome Brachmann-DeLange syndrome also maps to this region suggesting that the tumor suppressor gene and the locus for the dysmorphology syndrome may be the same gene. Thus the specific aims of this proposal are: 1) To isolate candidate cDNAs from within the D3S1212-D3S1246 region; 2) To character the candidate cDNAs for expression patterns consistent with osteosarcoma tumor suppressor gene activity; 3) To conduct mutational analysis in osteosarcoma tumors on those candidate cDNAs with expression patterns consistent with osteosarcoma tumor suppressor gene activity; 4) to conduct mutational analysis for inherited mutations in familial osteosarcoma and Brachmann-DeLange syndrome patients.