Genomic Predictors of Papillary Microcarcinoma Disease Progression

乳头状微小癌疾病进展的基因组预测因子

• 批准号: 8933080
• 负责人: Michael Berger
• 金额: $ 34.22万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8933080
• 关键词: Age; American; Archives; Automobile Driving; Autopsy; BRAF gene; Behavior; Benign; Biopsy; Canada; Clinical; Clinical Trials; Control Groups; Coupled; Custom; Data; Detection; Development; Diagnosis; Disease; Disease Progression; Distant; Distant Metastasis; Enrollment; Europe; Evaluation; Event; Excision; Exons; Fine needle aspiration biopsy; Freezing; Gender; Genes; Genetic Transcription; Genomics; Goals; Incidence; Indolent; Japan; Literature; Malignant Neoplasms; Malignant neoplasm of thyroid; Minority; Molecular; Molecular Profiling; Mutate; Mutation; Natural History; Nature; Neoplasm Metastasis; Oncogenes; Operative Surgical Procedures; Outcome; Papillary; Papillary thyroid carcinoma; Paraffin Embedding; Pathology; Patients; Physicians; Population; Primary Neoplasm; Proto-Oncogene Proteins c-akt; Recurrence; Reporting; Sampling; South America; System; Technology; Thyroid Gland; Thyroidectomy; Time; Tissue Sample; Treatment Effectiveness; United States; base; cancer genome; clinically significant; cohort; design; mortality; nano-string; next generation; next generation sequencing; patient population; prevent; prospective; screening; tumor

The incidence of thyroid cancer has more than doubled in the last 30 years with nearly 50% of this increase attributable to papillary microcarcinomas (PMC). Despite compeling evidence that cautious observation is a safe and effective alternative to immediate surgical resection, very few PMC patients in the United States are given the option of an active surveillance approach. This is in part due to reports in the literature of a small percentage of patients with PMC that develop loco-regional or distant metastases. Unfortunately, neither clinical features, nor the mutational status ofthe known thyroid cancer oncogenes reliably identify the few PMC patients destined to develop clinically significant disease progression. Since only a small minority of PMC progress to clinically significant disease, it is imperative that we critically re-evaluate the current management paradigm that indiscriminately recommends immediate surgical intervention without giving patients an option for active surveillance. We propose to use both paraffin embedded tissue samples from our pathology archives and fresh frozen PMC samples obtained after 2-5 years of observation in a prospective active surveillance trial to identify molecular events that are predictive of disease progression through a comprehensive evaluation of the PMC cancer genome using massively parallel next generation exon sequencing of 230 genes commonly mutated in cancer coupled to quantitative expression profiling using a custom-designed NanoString platform. Our goal is to identify genomic predictors of disease progression in PMC so that tumors likely to develop into clinically significant disease can be surgically removed, whereas the vast majority that are unlikely to grow or metastasize can be followed with periodic surveillance. Aim 1: To perform indepth genomic profiling of PMCs without metastatic disease compared to PMCs with loco-regional and/or distant metastasis. Aim 2: To identify genomic predictors of disease progression in a prospectively followed population of patients with PMC.

过去 30 年，甲状腺癌的发病率增加了一倍多，其中近 50% 的增幅 归因于乳头状微小癌（PMC）。尽管有令人信服的证据表明谨慎观察是 作为立即手术切除的安全有效的替代方案，美国很少有 PMC 患者接受 考虑到主动监测方法的选择。这部分是由于小型文献中的报告 PMC 患者发生局部或远处转移的百分比。不幸的是，两者都没有 临床特征或已知甲状腺癌癌基因的突变状态都不能可靠地识别少数甲状腺癌 PMC 患者注定会出现临床上显着的疾病进展。由于只有极少数 PMC 进展为具有临床意义的疾病，我们有必要批判性地重新评估当前的情况 不加区别地建议立即进行手术干预而不给予治疗的管理模式 患者可以选择主动监测。 我们建议使用来自我们病理档案的石蜡包埋组织样本和新鲜冷冻的组织样本 在前瞻性主动监测试验中观察 2-5 年后获得的 PMC 样本，以识别 通过对 PMC 的综合评估来预测疾病进展的分子事件 使用大规模并行下一代外显子测序对 230 个常见突变基因进行癌症基因组分析 使用定制设计的 NanoString 平台结合定量表达谱分析癌症。我们的 目标是确定 PMC 疾病进展的基因组预测因子，以便肿瘤可能发展为 临床上显着的疾病可以通过手术切除，而绝大多数不太可能生长或生长的疾病 可以定期监测转移情况。 目标 1：与有转移性疾病的 PMC 相比，对无转移性疾病的 PMC 进行深入的基因组分析 局部区域和/或远处转移。 目标 2：在前瞻性随访人群中确定疾病进展的基因组预测因子 PMC 患者。