Integration of Clinical and Molecular Biomarkers for Melanoma Survival

计划项目摘要/摘要 我们聚集了12个机构，以促进对生物的更好了解 黑色素瘤及其对个体生存的影响。我们的假设是，原发性黑色素瘤会有 黑色素瘤AJCC TNM分期的分子和临床特征 IIA/IIB/IIC/IIIA/IIIB，在几乎没有有效辅助治疗的情况下，向预后良好的患者和 预后不良。在这些阶段确诊的个人目前的死亡率在18- IIA/IIB/IIC期占47%，IIIA/IIIB期占32-78%。改善临床护理和 这些患者的预后可以通过专注于确定和确定优先顺序来实现 生物标志物--包括分子和临床--可能会对高危患者进行分类，以进行新的辅助治疗。 在这项研究中，我们将确定体细胞肿瘤突变、CNV、免疫图谱、甲基化图谱以及 原发黑色素瘤中与预后相关的microRNA/mRNAs特征，最终目的是 将这些信息转化为诊所，以实现个性化护理。目前，国内在这方面的研究还很匮乏。 黑色素瘤领域关注流行病学/基因组因素和黑色素瘤存活率。为了确认身份，确认 和开发这样的生物标记物，我们已经收集了9个处于AJCC TNM期的黑色素瘤患者 IIA/IIB/IIC/IIIA/IIIB，包括1000人，截至2012年已有500人死于疾病，500人 他们至少活了5年。患者将在分期上进行频率匹配。当我们将数据从 多个平台，我们将把数据集随机分成一个训练集(660个肿瘤，一半是侵袭性的，一半是侵袭性的 非侵袭性)和验证集(340个肿瘤，一半侵袭性，一半非侵袭性)。意义重大 培训集中的调查结果将在验证集中复制。这些患者都接受了 标准护理手术。这项研究中的所有患者都将有足够的肿瘤组织，生殖系DNA和临床， 记录病理和人口统计信息。 我们的目标是确定与生存相关的预后生物标记物。目标是确定患者是否患有 在发生转移之前进行更积极的治疗将是相关的，也就是说， 对它们的生存有影响。我们的中心假设是黑色素瘤的预后在很大程度上是在早期决定的。 肿瘤发生与DNA和RNA标志物，结合临床病理和蛋白质 原发黑色素瘤的特征将增加超越病理特征的预后预测信息 用于AJCC肿瘤分期。我们正在采取综合的方法来利用和组织 每个项目产生的大量信息。这些信息将提供给临床医生和 尽快与其他调查人员联系。

Program Project Abstract/Summary We have brought together 12 institutions in order to promote a better understanding of the biology of melanoma and how that affects an individual’s survival. Our hypothesis is that primary melanomas will have molecular and clinical features that will allow the stratification of melanoma tumors at AJCC TNM Stages IIA/IIB/IIC/IIIA/IIIB, where there is little effective adjuvant therapy, into those with a good prognosis and those with poor prognosis. The current mortality rate for individuals diagnosed at these stages ranges between 18- 47% for Stages IIA/IIB/IIC and 32-78% for Stage IIIA/IIIB patients. The ability to improve clinical care and patient outcomes for these patients might be achieved by focusing on the identification and prioritization of biomarkers – both molecular and clinical – that might triage high risk patients for new adjuvant therapies. In this study, we will identify somatic tumor mutations, CNVs, an immune profile, methylation profiles, and microRNA/mRNA signatures in primary melanoma that are associated with prognosis, with the ultimate intent of translating this information into the clinic to personalize care. Currently, there is a dearth of studies in the melanoma field looking at epidemiologic/genomic factors and melanoma survival. In order to identify, confirm and develop such biomarkers, we have brought together 9 cohorts of melanoma patients at AJCC TNM stages IIA/IIB/IIC/IIIA/IIIB, comprising 1000 individuals, 500 of whom have died from their disease as of 2012 and 500 whom have lived at least 5 years. Patients will be frequency matched for stage. As we integrate data from multiple platforms, we will randomly divide the dataset into a training set (660 tumors, half aggressive and half non-aggressive) and a validation set (340 tumors, half aggressive and half non-aggressive). Significant findings in the training set will be replicated in the validation set. These patients have all been treated using standard-of-care surgery. All patients in this study will have adequate tumor tissue, germline DNA and clinical, pathologic and demographic information recorded. Our objective is to identify prognostic biomarkers associated with survival. The goal is to identify patients for whom more aggressive therapy prior to developing metastases would be relevant, that is would make a difference to their survival. Our central hypothesis is that melanoma prognosis is largely determined early in tumor development and that DNA and RNA markers, combined with clinicopathologic and protein characteristics in primary melanoma will add information to outcome prediction beyond the pathologic features used in AJCC tumor staging. We are taking an integrative approach to take advantage of and organize the large amount of information generated from each project. Such information will be available to clinicians and other investigators as soon as possible.