Integration of Clinical and Molecular Biomarkers for Melanoma Survival

黑色素瘤生存的临床和分子生物标志物的整合

基本信息

批准号：
9278471
负责人：
MARIANNE BERWICK
金额：
$ 229.27万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9278471
关键词：
Aberrant DNA Methylation Adjuvant Therapy Affect Aggressive behavior American Joint Committee on Cancer BRAF gene Bioinformatics Biological Assay Biological Markers Biology CD3 Antigens CD8B1 gene CDKN2A gene Candidate Disease Gene Characteristics Clinic Clinical Copy Number Polymorphism CpG Island Methylator Phenotype DNA DNA Markers DNA Methylation Data Data Set Development Diagnosis Diagnostic Neoplasm Staging Disease Drug Targeting Epidemiology Event FOXP3 gene Frequencies Gene Expression Gene Expression Profile Genes Genetic Transcription Genomics Goals Heterogeneity Immune Individual Institution Joints Literature Malignant Neoplasms Messenger RNA Methods Methylation MicroRNAs Molecular Mutation NF1 mutation Neoplasm Metastasis Operative Surgical Procedures Outcome PDCD1LG1 gene PTEN gene Pathologic Patient risk Patient-Focused Outcomes Patients Predictive Factor Prior Therapy Process Prognostic Marker Proteins RNA marker Reproducibility Research Personnel Role Somatic Mutation Specimen Stage at Diagnosis Staging Staining method Stains Stratification Subgroup TNM Testing Time Tissues Training Translating Triage Tumor Tissue Validation aggressive therapy base clinical biomarkers clinical care clinical practice cohort high risk improved mRNA Expression melanoma melanoma biomarkers molecular marker molecular subtypes mortality nano-string novel outcome forecast outcome prediction personalized care predictive signature prognostic prognostic of survival prognostic signature programs protein expression response standard of care survival outcome survival prediction targeted sequencing tumor tumor heterogeneity

项目摘要

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.

程序项目摘要/摘要我们汇集了12个机构，以便更好地了解黑色素瘤及其如何影响个人的生存。我们的假设是主要黑色素瘤分子和临床特征将允许在AJCC TNM阶段分层黑色素瘤肿瘤 IIA/IIB/IIC/IIIA/IIIB（几乎没有有效的调整疗法）及时有很好的提示和那些疗法预后不良。在这些阶段诊断的人的当前死亡率在18-之间 IIA/IIB/IIC的阶段为47％，IIIA/IIIB患者为32-78％。改善临床护理和这些患者的患者预后可能是通过关注和优先级来实现的生物标志物（分子和临床）可能会为新的调整疗法而分类的高风险患者。在这项研究中，我们将确定体细胞肿瘤突变，CNV，免疫特征，甲基化谱和与预后相关的原发性黑色素瘤中的microRNA/mRNA特征，最终意图将这些信息转化为诊所以个性化护理。目前，研究死亡探讨流行病学/基因组因子和黑色素瘤存活率的黑色素瘤领域。为了识别，请确认并开发出这样的生物标志物，我们在AJCC TNM阶段汇集了9名黑色素瘤患者 IIA/IIB/IIC/IIIA/IIIB，完成了1000个人，其中500名因其疾病而死于2012年和500人他们至少生活了5年。患者将与阶段相匹配。当我们从多个平台，我们将随机将数据集分为一个训练集（660个肿瘤，一半侵略性和一半重要的培训集中的发现将在验证集中复制。这些患者均已使用护理标准手术。这项研究中的所有患者将具有足够的肿瘤组织，种系DNA和临床，记录了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志物。目标是确定患者在开发转移之前，他们更具侵略性的疗法是相关的，那就是与他们的生存不同。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确定的肿瘤发育以及DNA和RNA标记，结合临床病理学和蛋白质原发性黑色素瘤的特征将添加信息以超出病理特征的结果预测用于AJCC肿瘤分期。我们正在采用一种综合方法来利用并组织每个项目都会产生大量信息。此类信息将提供给临床医生和其他调查人员尽快。