DNA Methylation in Patients with Non-Hodgkin's Lymphoma

提出了分子生物学的技术进步，将新的诊断和治疗方法引入临床实践。除其他外，这些方法应该提高现有技术的灵敏度，足够强大，以允许对临床样本进行多参数评估，并且不应该要求样本采集的侵入性程序。在这项提案中，我们将测试现有现代技术的组合，该技术旨在提供对弥漫性大B细胞淋巴瘤的高通量、多参数检测。在项目的R21阶段，我们将使用患者的培养细胞和石蜡包埋组织来确定该分析的灵敏度、选择性和变异性。当R21阶段的里程碑达到时，我们将进入项目的临床R33阶段，测试该方法检测患者血浆中淋巴瘤特异性DNA的能力。我们将测试分析结果与弥漫性大B细胞淋巴瘤临床诊断的相关性，以及与临床结果的相关性，包括无病生存率和耐药性。当检测方法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效果监测的问题。

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.