IDENTIFICATION OF GENES AMPLIFIED IN THYROID TUMORS

甲状腺肿瘤中扩增基因的鉴定

• 批准号: 2429885
• 负责人: JEFFREY A KNAUF
• 金额: $ 3.12万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-22 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2429885
• 关键词: comparative genomic hybridization; complementary DNA; genetic library; genetic mapping; molecular cloning; molecular oncology; natural gene amplification; northern blottings; oncogenes; protein kinase C; thyroid neoplasm; tissue /cell culture

Each year in the United States 12,000 new cases of thyroid cancer are reported. Recently, somatic gene defects associated with the various human thyroid tumor phenotypes have been identified. However, the prevalence of these gene defects is low, suggesting that many oncogenic events are still to be identified. Gene amplification of oncogenes is a common mechanism of tumorigenesis. Comparative genomic hybridization (CGH) was used to determine chromosomal loci which are amplified in thyroid neoplasms. A discrete amplified locus on 2p21 has been mapped to a BAC clone which will be used to isolate candidate oncogenes. The size of the amplicon will be determined with contigs to this BAC. Exon trapping or other positional cloning strategies will be used to identify coding sequences from within this BAC and its contigs demonstrated to be part of the amplicon. These sequences will then be used to identify the corresponding cDNA from thyroid cDNA libraries. The cDNA will then be examined for expression in normal and tumor thyroid samples by probing a large panel of northern blots. Thyroid as well as other tumors will be examined for structural defects in this sequence. Finally, the possible function of these putative oncogenes will be studied using strategies that will be dictated in part by their sequence.

美国每年新增 12,000 例甲状腺癌病例 报道称。最近，体细胞基因缺陷与各种人类 甲状腺肿瘤的表型已被鉴定。然而，普遍存在 这些基因缺陷很低，表明许多致癌事件仍然存在 待识别。癌基因的基因扩增是常见的机制 肿瘤发生。 比较基因组杂交（CGH）被用来 确定在甲状腺肿瘤中扩增的染色体位点。一个 2p21 上的离散扩增基因座已被映射到 BAC 克隆，该克隆将 用于分离候选癌基因。扩增子的大小为 由该 BAC 的重叠群确定。外显子捕获或其他位置 克隆策略将用于从内部识别编码序列 该 BAC 及其重叠群被证明是扩增子的一部分。这些 然后将使用序列来识别相应的 cDNA 甲状腺 cDNA 文库。 然后将检查 cDNA 的表达情况 通过探测一大组北部地区的正常和肿瘤甲状腺样本 印迹。甲状腺以及其他肿瘤将接受结构检查 该序列中的缺陷。最后，这些假定的可能功能 将使用部分指定的策略来研究癌基因 按它们的顺序。