Molecular Classification of Primary Cutaneous Melanoma

原发性皮肤黑色素瘤的分子分类

• 批准号: 7258264
• 负责人: MOHAMMED KASHANI-SABET
• 金额: $ 29.24万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-04 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7258264
• 关键词: Appendix; Benign; Biological Markers; Cessation of life; Classification; Classification Scheme; Cutaneous Melanoma; Diagnosis; Diagnostic; Excision; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genes; Heterogeneity; Histologic; Histology; Human; Laboratories; Malignant - descriptor; Malignant Neoplasms; Melanocytic Neoplasm; Melanocytic nevus; Metastatic Melanoma; Microarray Analysis; Mole the mammal; Molecular; Molecular Profiling; Neoplasm Metastasis; Nevus; Numbers; Operative Surgical Procedures; Pathologic; Patients; Prognostic Marker; Proteins; Radial; Risk; Role; Sentinel Lymph Node; Sentinel Lymph Node Biopsy; Specimen; Staging; Testing; Time; Tissue Microarray; Tissue-Specific Gene Expression; Tissues; Validation; Vertical Growth Phase; base; cDNA Arrays; cancer classification; cohort; follow-up; lymph nodes; melanoma; novel; novel diagnostics; outcome forecast; protein expression; tumor progression

DESCRIPTION (provided by applicant): Gene expression profiling has the potential to revolutionize current approaches to cancer classification and diagnosis. Recent cDNA microarray analyses of moles, primary and metastatic melanomas performed in our laboratory have identified a number of genes whose expression level can be used to distinguish between known landmarks in the tumor progression cascade of melanoma. These studies have suggested the utility of gene expression profiling to develop a novel molecular classification of melanocytic neoplasms. In this application, we propose to extend these observations by developing a molecular classification of melanoma using gene expression profiling. We will also assess the utility of immunohistochemical analysis to develop molecular diagnostic and prognostic markers for melanoma. Our aims are: Aim 1: To classify the molecular subtypes of primary melanoma by gene expression profiling of a large cohort of melanoma patients. Aim 2: To assess the utility of immunohistochemical analysis of multiple molecular markers to differentiate primary melanomas from benign nevi. We will examine the protein expression of eight markers identified in our cDNA microarray analysis as being differentially expressed in melanomas when compared with nevi in a test set of 350 primary melanomas and 150 nevi, and a validation set of 75 cases of primary melanoma arising in a nevus. Aim 3: To assess the utility of immunohistochemical analysis of multiple molecular markers for their ability to predict the prognosis associated with melanoma. We will examine whether eight molecular markers identified in our cDNA microarray analysis as being differentially expressed in metastatic melanomas can predict melanoma prognosis when analyzed at the protein level. We will use immunohistochemical analysis to quantitate expression of these eight markers in a cohort of 353 primary melanomas with defined histology and follow up. Overall, these studies should more precisely characterize the molecular basis of melanoma heterogeneity, and identify novel diagnostic and prognostic markers for primary melanoma.

描述（由申请人提供）：基因表达谱有可能彻底改变当前的癌症分类和诊断方法。最近，我们实验室对痣、原发性和转移性黑色素瘤进行了 cDNA 微阵列分析，确定了许多基因，其表达水平可用于区分黑色素瘤肿瘤进展级联中的已知标志。这些研究表明基因表达谱可用于开发黑素细胞肿瘤的新分子分类。在此应用中，我们建议通过使用基因表达谱开发黑色素瘤的分子分类来扩展这些观察结果。我们还将评估免疫组织化学分析在开发黑色素瘤分子诊断和预后标记物方面的效用。我们的目标是： 目标 1：通过一大群黑色素瘤患者的基因表达谱对原发性黑色素瘤的分子亚型进行分类。目标 2：评估多种分子标记的免疫组织化学分析在区分原发性黑色素瘤和良性痣中的效用。我们将在 350 个原发性黑色素瘤和 150 个痣的测试组以及由 75 个痣中产生的原发性黑色素瘤病例组成的验证组中，检查 cDNA 微阵列分析中鉴定出的 8 个标记物的蛋白质表达，这些标记物在黑色素瘤中与痣相比存在差异表达。目标 3：评估多种分子标记物免疫组织化学分析在预测黑色素瘤相关预后方面的效用。我们将检查在 cDNA 微阵列分析中鉴定出的八种在转移性黑色素瘤中差异表达的分子标记在蛋白质水平上进行分析时是否可以预测黑色素瘤的预后。我们将使用免疫组织化学分析来定量 353 个具有明确组织学和随访的原发性黑色素瘤队列中这八种标记物的表达。总的来说，这些研究应该更准确地描述黑色素瘤异质性的分子基础，并确定原发性黑色素瘤的新诊断和预后标志物。