Oncogene Mutation Profiling in Uveal Melanoma

描述（由申请人提供）：尽管葡萄膜黑色素瘤的局部控制率很高，但由于缺乏对转移性疾病的治疗，葡萄膜黑色素瘤是最常见的眼内恶性肿瘤，在很大一部分患者中仍然是致命的。本应用程序提出了一个系统的搜索体细胞突变在葡萄膜黑色素瘤样本的一个大面板的癌症基因使用高通量，质谱为基础的基因分型技术。利用这项技术，我们将筛选超过100种致癌基因和肿瘤抑制基因的已知突变，以确定葡萄膜黑色素瘤中普遍存在的特定突变，建立特定突变与临床结果之间的相关性，并开始在体外确认这些突变的功能意义。这些研究将为开发合理设计的靶向辅助化疗提供重要的一步，这对于提高最常见的眼内恶性肿瘤患者的生存率是必要的。

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.