Microarray analysis of thyroid neoplasm

描述(申请人提供)：虽然细针吸取(FNA)细胞学是鉴别诊断甲状腺结节的最佳诊断工具，但它通常不能区分良恶性病变。因此，大多数甲状腺结节患者需要手术，因为可疑的，但不确定的，恶性肿瘤的诊断。由于良性和恶性甲状腺肿瘤的外科治疗不同，可疑FNAs的患者可能会以不太理想的方式进行手术治疗。虽然其他人和我们已经记录了甲状腺肿瘤的各种基因改变，但没有特定的改变(S)可以可靠地区分良恶性病变。我们认为，存在与不同甲状腺肿瘤类型相关的特定基因表达模式，这些不同的表达模式可以被用来区分不同的肿瘤类型。因此，我们建议通过基因芯片分析对可疑的甲状腺FNA样本中最常见的良性和恶性甲状腺病变进行基因分型。为了实现这些目标，我们提出了以下具体目标：具体目标1：通过使用包含37,000个基因的尼龙滤膜阵列进行综合的基因芯片分析，评估来自滤泡性腺瘤和相应正常甲状腺的甲状腺肿瘤样本。我们已经用这种方法评估了乳头状甲状腺癌。我们建议对滤泡性腺瘤进行同样的治疗。具体目的2：应用cDNA玻片阵列对滤泡性腺瘤、乳头状甲状腺癌和相应正常甲状腺组织中的单个甲状腺肿瘤标本进行检测。与特定目标1中描述的分析相一致，将通过聚类分析来分析数据，以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。这将通过对一组甲状腺肿瘤的RNA样本进行实时定量RT-PCR进行。

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.