Oncogene Mutation Profiling in Uveal Melanoma

描述（由申请人提供）：尽管局部控制率很高，但由于缺乏转移性疾病的治疗，葡萄膜黑色素瘤（最常见的眼内恶性肿瘤）在大部分患者中仍然是致命的。本申请提出了使用高通量、基于质谱的基因分型技术在葡萄膜黑色素瘤样本中的一大组癌症基因中系统地搜索体细胞突变。利用这项技术，我们将在100多个癌基因和肿瘤抑制基因中筛选已知的突变，以确定葡萄膜黑色素瘤中普遍存在的特定突变，建立特定突变和临床结果之间的相关性，并开始在体外证实这些突变的功能意义。这些研究将为开发合理设计的、有针对性的辅助化疗提供重要的一步，这些化疗是提高最常见眼内恶性肿瘤患者生存率所必需的。 公共卫生相关性：葡萄膜黑色素瘤是最常见的眼内癌症，目前，这种癌症一旦扩散到眼外就没有有效的治疗方法。该项目将在这种肿瘤类型中寻找100多种已知的致癌突变，希望找到新药的靶点，以提高这种恶性肿瘤患者的生存率。

DESCRIPTION (provided by applicant): Despite excellent rates of local control, uveal melanoma, the most common intraocular malignancy, remains lethal in a large proportion of patients due to the lack of treatments for metastatic disease. This application proposes a systematic search for somatic mutations in a large panel of cancer genes in uveal melanoma specimens using a high- throughput, mass spectrometry-based genotyping technology. Using this technology, we will screen for known mutations in over 100 oncogenes and tumor suppressor genes in order to identify specific mutations prevalent in uveal melanoma, establish correlations between particular mutations and clinical outcome, and begin to confirm the functional significance of these mutations in vitro. These studies will provide an important step towards development of rationally-designed, targeted adjuvant chemotherapy necessary for improved survival of patients with the most common intraocular malignancy. PUBLIC HEALTH RELEVANCE: Uveal melanoma is the most common intraocular cancer, and currently, there is no effective treatment for this cancer once it spreads outside the eye. This project will search for over 100 known cancer-causing mutations in this tumor type in hopes of finding targets for new drugs that will improve the survival of patients with this malignancy.