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，占人类所有恶性肿瘤的1%。然而，尸检研究表明，它的实际发生率可能高达10%。到目前为止，许多基因，包括癌基因(不适当地启动并参与肿瘤发展过程的基因)和肿瘤抑制基因(关闭并失去对肿瘤发展的保护作用的基因)，都与甲状腺癌的发生有关。然而，这些基因的突变，即遗传密码的错误，只占甲状腺肿瘤的一小部分，而且这些基因都没有被证明是肿瘤进展或侵袭性的明确预后标志。细胞遗传学(研究染色体)和分子遗传学(在DNA和RNA水平上研究基因)这两个领域的融合增强了我们理解肿瘤发展过程的能力。我们建议使用一种名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的肿瘤发展相关的新基因。这项技术已经被用来帮助定位在卵巢癌和脑癌以及一些以乳腺癌和胃肠道恶性肿瘤为特征的家族性综合征中起作用的基因。这种方法包括检测肿瘤DNA中的染色体扩增或缺失区域，这些DNA被荧光标记(绿色)，与正常的人类DNA混合也被荧光标记(红色)。如果肿瘤包含扩增区域(可能包含癌基因)，分析显示绿色荧光增强，如果存在缺失(可能包含肿瘤抑制基因)，分析显示红色荧光增强。通过这种方法确定的染色体区域将被进一步分析，以确定它们包含的准确基因，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.