Prognostic Markers for Primary Cutaneous Melanoma

原发性皮肤黑色素瘤的预后标志物

• 批准号: 6752467
• 负责人: DANIEL PINKEL
• 金额: $ 26.97万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6752467
• 关键词: biomarker; biopsy; cancer prevention; cancer risk; cell population study; diagnosis design /evaluation; fluorescent in situ hybridization; functional /structural genomics; gene expression; genetic markers; human genetic material tag; human tissue; immunocytochemistry; lymph nodes; melanoma; metastasis; microarray technology; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplastic cell; nucleic acid quantitation /detection; patient care planning; patient oriented research; prognosis; statistics /biometry

DESCRIPTION: (provided by applicant) Cutaneous melanoma presents a significant health problem in Western Europe, Australia, and the United States. Americans in the United States currently have approximately a 1 in 75 lifetime risk developing this disease. If melanoma is not excised before it metastasizes the prognosis is poor. Recent evaluation of adjuvant treatments such as interferon alpha indicate the ability to prolong survival in patients with occult metastases, so identification of these patients is highly important. The goal of this proposal is to develop DNA copy number and gene expression markers in the primary tumor that will improve the ability to determine if clinically significant metastasis has occurred by the time of diagnosis. Sentinel lymph node (SLN) biopsy, coupled with several other characteristics of the primary tumor such as thickness and ulceration, are currently the best prognostic indicators. The finding of malignant cells in a sentinel node is a definite sign that the disease has begun to spread. but negative nodes do not guarantee a good outcome. A substantial proportion of all cases of metastatic melanoma come from patients who were SNL- at diagnosis. Thus improving the ability to determine which patients were at elevated risk of progression would have substantial medical benefit. In this project we w ill study primary tumors and corresponding metastases from a cohort of 700 patients that underwent SLN biopsy at UCSF, and an additional set of 100 primary tumors of Acral Lentiginous Melanoma (ALM), to detect DNA copy number changes and gene expression changes that distinguish primary tumors that metastasize from those that do not. Screening for DNA copy aberrations will be performed using array comparative genomic hybridization (array CGH) which has recently been developed in our laboratories. Candidate genes will be identified based on the copy number aberrations, and the prognostic power of the expression levels of these candidates will be evaluated. Using an independent set of tumors from the SLN cohort, we will validate the ability of these markers to: 1) distinguish patients that develop metastases from those that do not, and 2) to distinguish patients with negative sentinel nodes that develop metastases from those with negative nodes that remain disease free.

描述：（由申请人提供）皮肤黑色素瘤表现出重要的 西欧，澳大利亚和美国的健康问题。美国人 在美国，目前大约有75个终身风险中的1个 发展这种疾病。如果黑色素瘤未在转移之前切除 预后很差。最近对辅助治疗（例如干扰素）的评估 alpha表示在神秘患者中延长生存的能力 转移，因此对这些患者的识别非常重要。目标 该建议的是开发DNA拷贝数和基因表达标记 将提高确定是否在临床上确定能力的主要肿瘤 在诊断时发生了明显的转移。 前哨淋巴结（SLN）活检，再加上其他几个特征 主要肿瘤（例如厚度和溃疡）目前是最好的 预后指标。在哨兵节点中发现恶性单元是一个 明确的迹象表明该疾病已经开始扩散。但是负节点没有 确保良好的结果。所有转移性病例中很大一部分 黑色素瘤来自患有诊断的患者。从而改善了 确定哪些患者的进展风险较高的能力将 拥有可观的医疗益处。在这个项目中，我们研究了原发性肿瘤 以及来自SLN的700名患者的队列中的相应转移 UCSF的活检和另外一组100个原发性肿瘤 弱性黑色素瘤（ALM），以检测DNA拷贝数变化和基因 表达变化，将转移与这些肿瘤的原发性肿瘤区分开 那不是。将使用数组进行DNA复制畸变的筛选 比较基因组杂交（阵列CGH），该杂交最近已开发 在我们的实验室。候选基因将根据副本确定 数字畸变以及这些表达水平的预后能力 将评估候选人。 使用来自SLN队列的独立肿瘤集，我们将验证 这些标记的能力：1）区分发展转移的患者 从那些没有的人和2）区分开哨兵的患者 从仍然存在负节点的淋巴结中发展转移的节点 无疾病。