Genetic determinants of Breslow tumor thickness and their impact on melanoma prog

Breslow 肿瘤厚度的遗传决定因素及其对黑色素瘤进展的影响

• 批准号: 8444849
• 负责人: Shenying Fang
• 金额: $ 7.9万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8444849
• 关键词: Affect; Antigens; Biological; Biological Markers; Breslow Thickness; Candidate Disease Gene; Categories; Cessation of life; Development; Disease Progression; Evaluation; Gene Expression Profiling; Genes; Genetic; Genetic Determinism; Genetic Polymorphism; Genetic Variation; Goals; Immunohistochemistry; Influentials; Localized Disease; Malignant Neoplasms; Molecular; Molecular Target; Neoplasm Metastasis; Outcome; Patients; Pattern; Polymorphism Analysis; Primary Neoplasm; Prognostic Factor; Recurrence; Relapse; Reporting; Research; Risk; Role; Single Nucleotide Polymorphism; Site; Staging; Testing; Thick; Tissue Microarray; Tissues; Translating; base; clinical practice; clinically significant; genetic variant; genome-wide; insight; mRNA Expression; melanocyte; melanoma; novel; outcome forecast; prognostic; public health relevance; treatment strategy; tumor

DESCRIPTION (provided by applicant): Melanoma is a rare, albeit potentially highly aggressive malignant tumor of melanocytes. Melanomas can spread quickly beyond the primary site at which they developed, they are highly curable if discovered and treated early. Primary tumor thickness has been considered to be the most influential prognostic factor in melanoma patients. No previous studies have reported an association between single nucleotide polymorphisms(SNPs) and tumor thickness or the biological roles of SNPs in melanoma progression. To determine whether common genetic variants that influence tumor thickness affect melanoma prognosis and also elucidate the molecular mechanism of disease progression, we propose to perform a coordinated genome-wide SNP analysis together with targeted gene expression analysis. We will test our hypothesis through the following aims: 1)To determine common genetic variants associated with Breslow tumor thickness among melanoma patients using genome-wide SNP analysis; 2)To examine expression patterns of candidate genes identified in Aim 1 using patient tissues with varying tumor thickness categories, via mRNA expression analysis and immunohistochemistry; and 3)To predict risk of melanoma recurrence and death on the basis of the SNPs identified in Aim 1. Identifying common genetic determinants of tumor thickness may provide new insights into prognosis in melanoma. Our findings will have a significant impact on the staging of melanoma and outcome prediction for melanoma patients who are at risk for relapse and metastasis, and provide clues for the development of new molecular targeted therapies.

描述(申请人提供)：黑色素瘤是一种罕见的，但潜在的高度侵袭性的恶性黑素细胞肿瘤。黑色素瘤可以迅速扩散到发生黑色素瘤的原发部位之外，如果及早发现和治疗，它们是高度可治愈的。原发肿瘤厚度被认为是影响黑色素瘤患者预后的最重要因素。以前没有研究报道单核苷酸多态(SNPs)与肿瘤厚度或SNPs在黑色素瘤进展中的生物学作用之间的关联。为了确定影响肿瘤厚度的常见遗传变异是否会影响黑色素瘤的预后，并阐明疾病进展的分子机制，我们建议进行协调的全基因组SNP分析和靶向基因表达分析。我们将通过以下目标验证我们的假设：1)使用全基因组SNP分析确定与Breslow肿瘤厚度相关的常见遗传变异；2)通过mRNA表达分析和免疫组织化学，使用不同肿瘤厚度类别的患者组织来检查Aim 1中确定的候选基因的表达模式；以及3)根据Aim 1中发现的SNPs预测黑色素瘤复发和死亡的风险。识别肿瘤厚度的常见基因决定因素可能为黑色素瘤预后提供新的见解。我们的发现将对黑色素瘤的分期和对有复发和转移风险的黑色素瘤患者的预后预测产生重大影响，并为开发新的分子靶向治疗提供线索。