PILOT--IDENTIFICATION OF COPY NUMBER ALTERATIONS IN ORAL CANCER

本研究拟采用一种新的细胞遗传学方法，即比较基因组学方法， 杂交（CGH），以确定新的遗传变异，在口腔 腔鳞状细胞肿瘤在比较基因组杂交中， 来自肿瘤的染色体DNA被均匀地标记为绿色 荧光染料和正常DNA用红色荧光染料标记。的 标记的DNA然后同时与正常人杂交， 中期扩散。绿色与红色荧光比率的定量 沿着每条染色体的长度， 减少的拷贝数将被识别和映射在一个单一的 实验该方法已成功地用于鉴定新的 非整倍性，扩增和缺失小到几个 兆。 50例口腔肿瘤标本按顺序进行CGH检查 以确定所有可能导致 在这种肿瘤类型中的肿瘤发生。初步数据表明，CGH可以 成功地进行了DNA提取固定，石蜡包埋 肿瘤组织和来自各种肿瘤的新鲜肿瘤标本 包括口腔肿瘤和肺肿瘤。确定的改动 CGH将与放疗疗效相关，定义如下： 局部控制肿瘤生长的效率。此外，小说 改变可能成为未来定位克隆的候选者 旨在确定基因的分子功能的努力 涉案

This study proposes to use a new cytogenetic method, comparative genomic hybridization (CGH), to identify novel genetic alterations in oral cavity squamous cell tumors. In comparative genomic hybridization, chromosomal DNA from tumors is uniformly labelled with a green fluorochrome and normal DNA is labelled with a red fluorochrome. The labelled DNAs are then simultaneously hybridized to normal human metaphase spreads. Quantitation of the green to red fluorescence ratio along the length of each chromosome allows regions of increased or decreased copy number to be identified and mapped in a single experiment. The method has been used successfully to identify novel aneuploidies, amplifications and deletions as small as several megabases. Fifty specimens of oral cavity tumors will be examined by CGH in order to identify all cytogenetic alterations that may contribute to tumorigenesis in this tumor type. Preliminary data indicate that CGH can be successfully performed on DNA extracted from fixed, paraffin-embedded tumor tissue and from fresh tumor specimens from a variety of tumors including oral cavity tumors and lung tumors. Alterations identified by CGH will be correlated with efficacy of radiotherapy as defined by efficiency of local control of tumor growth. In addition, novel alterations could become candidates for future positional cloning efforts designed to determine the molecular function of the gene(s) involved.