Diversity Supplement for Molecular Predictive Testing in Ocular Melanoma

眼部黑色素瘤分子预测测试的多样性补充

• 批准号: 10220448
• 负责人: JAMES WILLIAM HARBOUR
• 金额: $ 3.91万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220448
• 关键词: Adjuvant Therapy; Asses; Benign; Biological Markers; Blood specimen; Cessation of life; Disease; Funding; Gene Expression Profile; Grant; Industry Standard; Malignant - descriptor; Measurable; Melanocytic Neoplasm; Messenger RNA; Metastatic to; MicroRNAs; Micrometastasis; Molecular; Mutation; Ocular Melanoma; Patients; Primary Neoplasm; Research; Risk; Systemic Therapy; Testing; Uveal Melanoma; base; high risk; improved; innovation; malignant neoplasm of eye; patient stratification; personalized genomic medicine; predictive test; prognostic; prognostic assays; prognostic value; programs; prospective

Project Summary Uveal melanoma (UM) is a highly aggressive eye cancer that leads to metastatic death in up to half of patients. UM has a propensity to undergo early micrometastasis prior to treatment of the primary tumor, with later emergence of overt metastatic disease. Consequently, there has been no measurable improvement in survival over the past half century. The overall objective of our research program is to improve survival by developing highly accurate prognostic tests, based on biomarkers we discovered in the lab. In this proposal, we propose to (1) stratify patients with high-risk medium and large UMs to adjuvant therapy and increased metastatic surveillance, and (2) stratify patients with high-risk small UMs to early preemptive treatment of the primary tumor. During previous funding periods, we developed a highly innovative UM gene expression profile-based prognostic test (UM-GEP) that has been commercialized and is now used by a majority of centers in the US and beyond, to asses metastatic risk and make management decisions. Despite being recognized as the first- in-class industry standard in the field, there is a critical need to further improve its prognostic accuracy. We have since discovered new prognostically significant mutations in BAP1 and SF3B1 and a new mRNA biomarker (PRAME) that will set a new standard for prognostic accuracy, while also guiding the choice of systemic therapy. In this competitive renewal, we propose (1) to perform a landmark prospective 28-center study to optimize and validate these new biomarkers to expand the prognostic ability of the UM-GEP test and guide the choice of systemic therapy, and (2) to develop a ground breaking new prognostic test based on circulating exosomal microRNA profiling performed on routine blood samples, which will greatly expand the number of patients with benign and malignant uveal melanocytic tumors who will directly benefit from this personalized genomic medicine approach. 7

项目摘要 葡萄膜黑色素瘤(UM)是一种高度侵袭性的眼癌，可导致多达一半的患者发生转移性死亡。 UM有在原发肿瘤治疗前经历早期微转移的倾向， 出现明显的转移性疾病。因此，存活率没有明显的改善。 在过去的半个世纪。我们研究计划的总体目标是通过发展 基于我们在实验室中发现的生物标志物的高度准确的预后测试。在这项提案中，我们建议 (1)对高危、中型和大中型UM患者进行分层辅助治疗，并增加转移 监测，和(2)对高危小肠炎患者进行分层，以早期先发制人的初级治疗 肿瘤。在之前的资助期间，我们开发了一种基于UM基因表达谱的高度创新的 预后测试(UM-GEP)已经商业化，现在美国大多数中心都在使用 评估转移性风险并做出管理决策。尽管被认为是第一个- 在业内同类行业标准中，迫切需要进一步提高其预测准确性。我们 自那以后在BAP1和SF3B1以及一种新的mRNA中发现了新的具有预后意义的突变 生物标记物(PRAME)将为预后准确性设定新的标准，同时也指导选择 系统治疗。在这次竞争性更新中，我们建议(1)执行一个具有里程碑意义的预期28中锋 优化和验证这些新的生物标志物以扩大UM-GEP检测和预测能力的研究 指导全身治疗的选择，以及(2)开发一种开创性的新预后测试，其基础是 对常规血液样本进行循环外体microRNA分析，这将大大扩大 将直接受益于此的良性和恶性葡萄膜黑素细胞瘤患者的数量 个性化基因组医学方法。 7.

项目成果

Epigenetic reprogramming of melanoma cells by vitamin C treatment.

通过维生素C治疗对黑色素瘤细胞的表观遗传重编程。

• DOI: 10.1186/s13148-015-0087-z
• 发表时间: 2015
• 期刊: Clinical epigenetics
• 影响因子: 5.7
• 作者: Gustafson CB;Yang C;Dickson KM;Shao H;Van Booven D;Harbour JW;Liu ZJ;Wang G
• 通讯作者: Wang G

PRAME as an Independent Biomarker for Metastasis in Uveal Melanoma.

• DOI: 10.1158/1078-0432.ccr-15-2071
• 发表时间: 2016-03-01
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Field MG;Decatur CL;Kurtenbach S;Gezgin G;van der Velden PA;Jager MJ;Kozak KN;Harbour JW
• 通讯作者: Harbour JW

Intraocular Dissemination of Uveal Melanoma Cells Following Radiotherapy: Evolving Management Over the Past Decade.

放射治疗后葡萄膜黑色素瘤细胞的眼内播散：过去十年管理的演变。

• DOI: 10.3928/23258160-20190905-06
• 发表时间: 2019
• 期刊: Ophthalmic surgery, lasers & imaging retina
• 作者: Paez-Escamilla,Manuel;Walter,ScottD;Mohsenin,Amir;Decatur,ChristinaL;Harocopos,GeorgeJ;Dubovy,Sander;Harbour,JWilliam
• 通讯作者: Harbour,JWilliam

Gene Expression Profiling and PRAME Status Versus Tumor-Node-Metastasis Staging for Prognostication in Uveal Melanoma.

• DOI: 10.1016/j.ajo.2018.07.045
• 发表时间: 2018-11
• 期刊: American journal of ophthalmology
• 影响因子: 4.2
• 作者: Cai L;Paez-Escamilla M;Walter SD;Tarlan B;Decatur CL;Perez BM;Harbour JW
• 通讯作者: Harbour JW

ChIPprimersDB: a public repository of verified qPCR primers for chromatin immunoprecipitation (ChIP).

• DOI: 10.1093/nar/gky813
• 发表时间: 2019-01-08
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Kurtenbach S;Reddy R;Harbour JW
• 通讯作者: Harbour JW