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: 8738869
• 负责人: Michael Berger
• 金额: $ 31.4万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-19 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8738869
• 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.

甲状腺癌的发病率在过去的30年中增加了一倍多，其中近50%的发病率增加 乳头状微小癌（PMC）。尽管有令人信服的证据表明，谨慎的观察是一种 安全有效的替代立即手术切除，在美国很少有PMC患者 因为我们可以选择主动监视这在一定程度上是由于文献中有少量报道 发生局部区域或远处转移的PMC患者百分比。不幸的是， 临床特征和已知甲状腺癌癌基因的突变状态都不能可靠地确定少数 PMC患者注定发生具有临床意义的疾病进展。因为只有一小部分 如果PMC进展为具有临床意义的疾病，我们必须严格重新评估当前的情况 管理模式，不加区别地建议立即手术干预，而不给予 患者可以选择主动监测。 我们建议使用病理学档案中的石蜡包埋组织样本和新鲜冷冻组织样本。 在前瞻性主动监测试验中观察2-5年后获得PMC样本，以确定 通过对PMC的综合评价预测疾病进展的分子事件 使用230个通常突变的基因的大规模平行下一代外显子测序的癌症基因组 在癌症中，使用定制设计的NanoString平台结合定量表达谱分析。我们 目的是确定PMC疾病进展的基因组预测因子，以便肿瘤可能发展为 具有临床意义的疾病可以通过手术切除，而绝大多数不太可能生长或 可以通过定期监测来跟踪转移。 目的1：与具有转移性疾病的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。 目的2：在前瞻性随访的人群中确定疾病进展的基因组预测因子。 PMC患者