DNA Methylation in Patients with Non-Hodgkin's Lymphoma

分子生物学的技术进步为临床实践带来了新的诊断和治疗方法。除其他事项外，这些方法应改善现有技术的灵敏度，足够稳健以允许临床样品的多参数评估，并且不应需要用于样品采集的侵入性程序。在本提案中，我们将测试现有现代技术的组合，其旨在提供弥漫性大B细胞淋巴瘤的高通量、多参数检测。在项目的R21阶段，我们将使用培养的细胞和石蜡包埋的患者组织来确定检测的灵敏度、选择性和变异性。当达到R21阶段的里程碑时，我们将进入该项目的临床R33阶段，测试该检测试剂盒检测患者血浆中淋巴瘤特异性DNA的能力。我们将测试检测结果与弥漫性大B细胞淋巴瘤临床诊断的相关性，以及与临床结局的相关性，包括无病生存率和耐药性。当检测试剂盒针对患者血浆中的疾病检测进行优化时，我们还将解决残留疾病检测和治疗疗效监测的问题。

Technological advances of molecular biology are posed to bring new methods of diagnosis and treatment to clinical practice. Among other things these methods should improve on the sensitivity of existing techniques, be sufficiently robust to allow multi-parametric evaluation of clinical samples, and should not require invasive procedures for sample acquisition. In this proposal we will test a combination of existing modern techniques, which is designed to provide high-throughput, multi- parametric detection of diffuse large B-cell lymphoma. In R21 phase of the project we will use cultured cell and paraffin-embedded tissues of patients to determine sensitivity, selectivity and variability of the assay. When the milestones of R21 phase are met we will move into clinical R33 phase of the project, testing the assay's ability to detect lymphoma- specific DNA in patient's plasma. We will test correlation of the assay's results with clinical diagnosis of diffuse large B-cell lymphoma, and with clinical outcomes, including disease-free survival and drug resistence. When the assay is optimized for disease detection in patient's plasma we will also address the issue of residual disease detection and monitoring of treatment efficacy.