Microarray analysis of thyroid neoplasm

描述（由申请人提供）：虽然细针穿刺（FNA）细胞学是甲状腺结节鉴别诊断的最佳诊断工具，但它往往不能区分良性和恶性病变。因此，大多数甲状腺结节患者需要手术，因为可疑的，但不是明确的恶性诊断。由于良性和恶性甲状腺肿瘤的手术治疗不同，可疑的FNAs患者可能采用不太理想的手术治疗方式。虽然其他人和我们已经记录了甲状腺肿瘤的各种遗传改变，但没有特定的改变可以可靠地区分良性和恶性病变。我们提出存在与各种甲状腺肿瘤类型相关的特定基因表达模式，并且这些不同的表达模式可以被用来区分一种肿瘤类型。因此，我们建议通过cDNA微阵列分析对可疑甲状腺FNA样本中最常见的良性和恶性甲状腺病变进行基因分型。具体目的1：利用含有37,000个基因的尼龙过滤阵列，对滤泡腺瘤和相应的正常甲状腺肿瘤样本进行综合cDNA微阵列分析。我们已经用这种方法评估了甲状腺乳头状癌。我们建议对滤泡性腺瘤采用同样的治疗方法。特异性目的2：利用cDNA玻片阵列对滤泡腺瘤、乳头状甲状腺癌和相应的正常甲状腺的个体甲状腺肿瘤样本进行评价。与具体目标1中描述的分析相一致，将分析数据，通过聚类分析发现这些肿瘤中一致的基因表达模式。具体目标3：通过单独测量选定基因的表达水平来独立验证阵列分析的结果。这将使用定量实时RT-PCR对一组甲状腺肿瘤的RNA样本进行检测。

DESCRIPTION (provided by applicant): Although fine needle aspiration (FNA) cytology is the best diagnostic tool in the differential diagnosis of a thyroid nodule, it often cannot differentiate a benign from a malignant lesion. Consequently, a majority of patients with thyroid nodules require surgery because of a suspicious, but not definitive, diagnosis of malignancy. Because the surgical management for benign and malignant thyroid neoplasms differ, patients with suspicious FNAs may be treated in a less than ideal fashion surgically. Although others and we have documented various genetic alterations in thyroid neoplasms, no specific alteration(s) can reliably distinguish benign from malignant lesions. We propose that there are specific gene expression patterns associated with the various thyroid tumor types and that these differing expression patterns can be capitalized upon to differentiate one tumor type from another. We therefore propose to genotype the most common benign and malignant thyroid lesions that present as suspicious thyroid FNA samples by cDNA microarray analysis. To accomplish these goals we propose the following: Specific Aim 1: To evaluate pooled thyroid tumor samples from follicular adenomas and corresponding normal thyroid by comprehensive cDNA microarray analysis using nylon filter arrays containing 37,000 genes. We have evaluated papillary thyroid cancers with this approach. We propose the same for follicular adenomas. Specific Aim 2: To evaluate individual thyroid tumor samples from follicular adenomas and papillary thyroid cancers and corresponding normal thyroid using cDNA glass slide arrays. In concert with the analysis described under specific aim 1, data will be analyzed to discover consistent gene expression patterns in these tumors by cluster analysis. Specific Aim 3: To independently validate the results of the array analysis by measuring expression levels of selected genes individually. This will be performed using quantitative real-time RT-PCR on RNA samples from a panel of thyroid tumors.