IDENTIFICATION OF GENES AMPLIFIED IN THYROID TUMORS

美国每年新增12，000例甲状腺癌病例 报道近年来，体细胞基因缺陷与各种人类 甲状腺肿瘤的表型已经确定。然而， 这些基因缺陷是低的，这表明许多致癌事件仍然存在。 待鉴定癌基因的基因扩增是一种常见的机制， 肿瘤发生 比较基因组杂交（CGH）被用于 确定在甲状腺肿瘤中扩增的染色体位点。一 2p21上的离散扩增位点已定位到BAC克隆， 用于分离候选致癌基因。扩增子的大小将是 用这个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 然后将序列用于鉴定相应的cDNA， 甲状腺cDNA文库。 然后将检测cDNA的表达， 正常和肿瘤甲状腺样品通过探测一个大面板的北方 污点。甲状腺以及其他肿瘤将检查结构 这个序列的缺陷。最后，这些假定的可能功能 癌基因的研究将使用的策略，将部分决定 根据它们的序列

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.