Genetic Cytology for Ovarian and Endometrial Cancer Screening

卵巢癌和子宫内膜癌筛查的遗传细胞学

• 批准号: 9341921
• 负责人: ISAAC A KINDE
• 金额: $ 91.08万
• 依托单位: PAPGENE, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-01 至 2019-07-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9341921
• 关键词: Abnormal Cell; Advanced Development; Applications Grants; Award; BRCA1 gene; BRCA2 gene; Biological Assay; Biopsy; CLIA certified; Calibration; Cancer Detection; Cancer Diagnostics; Cancer Etiology; Cells; Cellular Morphology; Cessation of life; Clinical; Clinical Sensitivity; Contractor; Coupling; Cytology; DNA; DNA Sequence Alteration; Data; Detection; Disease; Early Diagnosis; Endometrial; Endometrial Carcinoma; Enrollment; Evaluation; Future; Genetic; Genotype; Gold; Guidelines; Hemorrhage; High Risk Woman; Imagery; Inherited; Laboratories; Light; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of ovary; Maryland; Massive Parallel Sequencing; Methods; Mutation; Mutation Analysis; Names; Operative Surgical Procedures; Ovarian; Pap smear; Patient risk; Patients; Phase; Pilot Projects; Postmenopause; Primary Neoplasm; Probability; Problem Solving; Prospective Studies; Prospective cohort; Publishing; Reference Values; Research; Resected; Retrospective Studies; Risk; Salpingo-Oophorectomy; Sampling; Screening for Endometrial Cancer; Screening for Ovarian Cancer; Sensitivity and Specificity; Services; Side; Specificity; Specimen; Technology; Testing; Tissues; Tumor Tissue; United States; Universities; Validation; Woman; base; cohort; commercialization; high risk; innovation; light microscopy; mutant; mutational status; patient safety; performance tests; phase 1 study; phase 2 study; prospective; public health relevance; screening; success; unpublished works; validation studies

 DESCRIPTION (provided by applicant): In this Fast Track application, a path to commercialization will be pursued for a breakthrough "genetic cytology" test capable of detecting both ovarian and endometrial cancer from routinely collected Pap specimens. In deference to the notable success of the Pap test in reducing deaths due to cervical cancer, and in reference to the core enabling genetic sequencing technology, this new test has been named PapGene. The PapGene test detects ovarian and endometrial cancers by applying newly affordable sequencing technology to Pap specimens; specimens that are safely and routinely collected from 50 million women each year in the United States. The PapGene test is a genetic cytology assay that achieves sensitivity and specificity through identifying DNA mutations causative of cancer from routinely collected clinical specimens. With traditional cytology (e.g., Pap testing), cells are subjectively analyzed for abnormal cell morphology through visualization by light microscopy. The PapGene test allows cells to be analyzed objectively with a massively parallel sequencing-based assay. The test uses a proprietary sequencing error-reducing strategy to accommodate the relatively low proportions of cancer-derived DNA that may exist in clinical specimens. In Phase I, this study will determine the accuracy, precision, analytical sensitivity, analytical specificity, reportable range, and reference range of the PapGene genetic cytology assay (Aim 1). A retrospective study will also be completed on previously-collected samples to demonstrate the clinical validity of the PapGene assay (Aim 2). In Phase II, this study will demonstrate clinical utility of the PapGene test for women at high risk for ovarian and endometrial cancer. A prospective study will be completed by applying the PapGene assay to two prospective cohorts - patients with postmenopausal bleeding undergoing endometrial biopsy and patients with a germline BRCA1 or BRCA2 undergoing Risk Reducing Salpingo-Oophorectomy (RRSO) (Aim 3). Regulatory approval for the PapGene test will be pursued by establishing a CLIA-certified laboratory for high-complexity testing to allow for commercial use of a Laboratory Developed Test (LDT). Discussions with the FDA will be started regarding premarket clearance and approval for the PapGene test to allow for more widely distributed use (Aim 4).

 描述（由申请人提供）：在这一快速通道申请中，将寻求一种突破性的“遗传细胞学”检测的商业化途径，该检测能够从常规收集的巴氏标本中检测卵巢癌和子宫内膜癌。鉴于巴氏试验在减少宫颈癌死亡方面取得的显著成功，并参考核心的基因测序技术，这种新的试验被命名为PapGene。PapGene检测通过将新的负担得起的测序技术应用于Pap标本来检测卵巢癌和子宫内膜癌;在美国，每年从5000万妇女中安全和常规地收集标本。PapGene检测是一种遗传细胞学检测，通过从常规收集的临床标本中识别致癌DNA突变来实现灵敏度和特异性。使用传统的细胞学（例如，巴氏试验），通过光学显微镜观察，主观分析细胞的异常细胞形态。PapGene检测允许通过大规模平行测序分析客观地分析细胞。该测试使用专有的测序错误减少策略，以适应临床标本中可能存在的相对较低比例的癌症衍生DNA。在I期，本研究将确定PapGene遗传细胞学检测试剂盒的准确度、精密度、分析灵敏度、分析特异性、可报告范围和参考范围（目的1）。还将对先前采集的样本进行回顾性研究，以证明PapGene检测试剂盒的临床有效性（目的2）。在第二阶段，这项研究将证明PapGene测试对卵巢癌和子宫内膜癌高风险女性的临床实用性。将通过将PapGene检测应用于两个前瞻性队列来完成前瞻性研究-接受子宫内膜活检的绝经后出血患者和接受风险降低输卵管卵巢切除术（RRSO）的生殖系BRCA 1或BRCA 2患者（目标3）。PapGene检测的监管批准将通过建立CLIA认证的高复杂性检测实验室来实现，以允许实验室开发检测（LDT）的商业用途。将开始与FDA讨论PapGene测试的上市前许可和批准，以允许更广泛的使用（目标4）。