The identification of novel genes involved in the initiation and development of thyroid neoplasia

甲状腺癌是最常见的内分泌恶性肿瘤，占所有人类恶性肿瘤的1%。然而，尸检研究表明其实际发生率可能高达10%。迄今为止，许多基因，包括癌基因（不适当地开启并参与肿瘤发展过程的基因）和肿瘤抑制基因（关闭并失去其对肿瘤发展的保护作用的基因），都与甲状腺癌的发展有关。然而，这些基因的突变，遗传密码中的错误，只占甲状腺肿瘤的一小部分，并且这些基因中没有一个被证明是有用的，作为肿瘤进展或侵袭性的明确预后标志物。细胞遗传学（染色体研究）和分子遗传学（DNA和RNA水平的基因研究）两个领域的合并加强了我们理解肿瘤发展过程的能力。我们建议使用一种称为比较基因组杂交的技术来帮助识别与良性和恶性甲状腺疾病中肿瘤发展相关的新基因。这项技术已经被用于帮助定位在卵巢癌和脑癌以及以乳腺癌和胃肠道恶性肿瘤为特征的一些家族性综合征中起作用的基因。该方法涉及检测荧光标记（绿色）的肿瘤DNA中染色体扩增或缺失的区域，该肿瘤DNA与同样荧光标记（红色）的正常人DNA混合。如果肿瘤含有扩增区域（可能含有致癌基因），分析显示绿色荧光增加，如果存在缺失（可能含有肿瘤抑制基因），分析显示红色荧光增加。通过这种方法鉴定的染色体区域将被进一步分析，以确定它们所包含的精确基因，并确定这些基因在甲状腺肿瘤发展中的作用。

Thyroid cancer is the most frequently diagnosed endocrine malignancy, comprising 1% of all human malignancy. However, its actual occurrence indicated by autopsy studies may be as high as 10%. To date, a number of genes, both oncogenes (genes that are inappropriately switched on and take part in the process of tumour development) and tumour suppressor genes (genes that are switched off and lose their protective role against tumour development), have been implicated in the development of thyroid cancer. However mutations, mistakes in the genetic code, of these genes account for only a small percentage of thyroid tumours and none of these genes have been shown to be useful as clear prognostic markers for tumour progression or aggressiveness. The merging of the 2 fields of cytogenetics (the study of chromosomes) and molecular genetics (the study of genes at the DNA and RNA level) has strengthened our ability to understand the process of tumour development. We are proposing use of a technique called Comparative Genomic Hybridisation to aid in the identification of new genes associated with tumour development in both benign and malignant thyroid disease. This technique has already been used to aid in the location of genes with a role in ovarian and brain cancer and in some familial syndromes characterised by breast and gastrointestinal malignancies. This method involves the detection of regions of chromosomal amplifications or deletions in tumour DNA that is fluorescently labelled (green), mixed with normal human DNA also fluorescently labelled (red). If the tumour contains regions of amplification (likely housing an oncogene), analyses show increased green fluorescence and if deletions are present (likely housing a tumour suppressor gene), analyses show increased red fluorescence. Chromosomal regions identified by this method will be further analysed to identify the precise genes they contain and establish a role for these genes in the development of thyroid tumours.