PROGNOSTIC MARKERS FOR ASSESSMENT OF TREATMENT EFFICACY OF MELANOMA

描述（由申请人提供）：管理中的主要问题之一 恶性黑色素瘤是预测疾病进展的过程后， 切除原发性肿瘤。我们的主要假设是分子标记 可用于分析肿瘤和血液，作为预测疾病的替代品 进展和结局，以及治疗疗效， 临床病理学事件。恶性黑色素瘤进展发生于 多种遗传变异的积累，导致进行性 遗传不稳定性为了将其检测和预后价值 这些变化的有效性，分析必须进行标本从 明确的回顾性和前瞻性临床试验。验证 分子结果将允许更好的疾病分层和管理， 恶性黑素瘤在上一个资助期，我们开发了多标记RTPCR 鉴定血液预后分子标志物（PMM）的测定， 表明它们可以作为亚临床的潜在替代物， 疾病进展，并预测疾病复发。我们将继续 在本提案中开发新的血液信息PMM。我们的假设是 包括黑色素瘤相关抗原的PMMs的定量水平 （MAAs）和影响肿瘤的细胞生理因素 黑色素瘤肿瘤的进展/转移也可用作 疾病结果和主动特异性免疫疗法（疫苗）的疗效。 我们的假设是原发性和转移性黑色素瘤的DNA标记物也可以 用作PMMs。我们发现了几个DNA标记 潜在的临床病理学效用。在这次更新中，我们将重点关注 评估配对的原发性/转移性黑色素瘤以发展不同类型的 PMM补充血液RT-PCR检测，与疾病进展相关 以及治疗失败的风险。 该项目的目标如下：1）开发和评估新的 用于评估黑色素瘤患者的肿瘤和血液的mRNA PMM; 2）发育和 评估黑色素瘤肿瘤中的DNA标记物作为黑色素瘤预后指标 疾病进展和结果;以及3）临床和 RNA和DNA分子标记在黑色素瘤中的病理学应用 入组多中心PMCV III期临床试验的患者。目标 将利用JWCI的大型黑色素瘤患者转诊， 全面的后续行动，为制定和评估项目管理办法提供资源。的 Aims还将利用随机多中心疫苗试验的优势， 存档并前瞻性采集标本，以验证PMM。 不同时期黑色素瘤分子标志物的鉴定 疾病进展将使我们能够开发一种“适用的”分子 发展模式，以帮助管理决策。

DESCRIPTION (provided by applicant): One of the major problems in managing malignant melanoma is predicting the course of disease progression after removal of the primary tumor. Our main hypothesis is that molecular markers can be used for analysis of tumors and blood as surrogates to predict disease progression and outcome, and treatment efficacy well in advance of clinicopathological events. Malignant melanoma progression occurs from accumulation of multiple genetic aberrations that result in progressive genetic instability. In order to translate the detection and prognostic value of these changes efficiently, analysis must be conducted on specimens from well-defined retrospective and prospective clinical trials. Validation of the molecular results will allow better disease stratification and management of malignant melanoma. In the previous grant period we developed multimarker RTPCR assays to identify blood prognostic molecular markers (PMMs) and demonstrated that they could be useful as potential surrogates of subclinical disease progression, and to predict disease recurrence. We will continue to develop new informative PMMs for blood in this proposal. Our hypothesis is that quantitative levels of PMMs which include melanoma-associated antigens (MAAs) and cellular physiologic factors influencing tumor progression/metastasis in melanoma tumors can also be used as surrogates of disease outcome and the efficacy of active-specific immunotherapy (vaccine). Our hypothesis is that DNA markers in primary and metastatic melanoma can also be used as PMMs. We have identified several DNA markers that have shown potential clinicopathological utility. In this renewal we will focus on assessing paired primary/metastatic melanomas to develop different types of PMMs to complement the blood RT-PCR assay as correlates to disease progression and outcome, and treatment failure. The Aims of the project are as follows: 1) Development and assessment of new mRNA PMMs for assessing melanoma patients' tumor and blood; 2) Development and assessment of DNA markers in melanoma tumors as prognostic indicators of disease progression and outcome; and 3) Validation of the clinical and pathological utility of RNA and DNA molecular markers in melanomas from patients entered in the multicenter PMCV Phase III clinical trial. The Aims will take advantage of the JWCI's large melanoma patient referral and comprehensive follow up to provide resources to develop and assess PMMs. The Aims will also take advantage of the randomized multicenter vaccine trial's archived and prospectively collected specimens to validate the PMMs. Identification of molecular markers for melanoma at different stages of disease progression will allow us to develop an "applicable" molecular progression model to aid in management decisions.