Urine based circulating tumor DNA analysis

摘要 尿液是非泌尿生殖道肿瘤患者全身循环肿瘤DNA的一个未被充分认识的来源 癌的基于最近的数据表明，基于血液的HPV DNA检测对疾病监测是有用的 在HPV阳性的口咽癌患者中，我们发现非转移性HPV阳性的口咽癌 患者作为一个很好的模型系统，以检查基于尿液的跨肾DNA分析的潜力。我们 初步数据表明，我们新开发的尿液HPV检测可能具有生物标志物性能， 与基于血液的HPV检测相比， 本申请的具体目的是确定尿液是非HPV感染中HPV DNA的合适来源。 转移性HPV阳性口咽癌患者，在家尿液分子检测是可行的 对于这些患者。具体来说，我们将比较治疗前尿中HPV检测的敏感性和特异性。 在新诊断的非转移性口咽癌队列中进行组织金标准检测 患者基于尿液的HPV检测的复发检测提前时间将与临床常规护理进行比较， 同一队列接受根治性治疗后。控制将包括基于血液的HPV检测，咽部 基于拭子的HPV检测和基于血液的个性化ctDNA测序面板检测。附加控制 队列将包括宫颈癌和肛门癌患者以及最近诊断为 致癌性HPV感染。使用体内荧光成像技术，我们将产生基本的 了解肾脏处理细胞游离DNA的知识，并确定慢性肾脏疾病和其他疾病的影响 患者、疾病和医源性因素对细胞游离DNA排泄的影响。

ABSTRACT Urine is an underappreciated source for systemic circulating tumor DNA in patients with non-genitourinary cancers. Based on recent data suggesting that blood-based HPV DNA testing is useful for disease monitoring in HPV positive oropharynx cancer patients, we identified non-metastatic HPV positive oropharyngeal cancer patients as an excellent model system to examine the potential of urine-based transrenal DNA analysis. Our preliminary data suggests that our newly developed urine-based HPV test could have biomarker performances comparing favorably to blood-based HPV testing. The specific objectives of this application are to establish that urine is a suitable source for HPV DNA in non- metastatic HPV positive oropharynx cancer patients, and that at-home urine based molecular testing is feasible for these patients. Specifically, we will compare sensitivity and specificity of pre-therapy urine-based HPV testing to tissue gold standard testing in a cohort of newly diagnosed non-metastatic oropharyngeal cancer patients. Recurrence detection lead time of urine-based HPV testing will be compared to clinical routine care in the same cohort after curative intent treatment. Controls will include blood-based HPV testing, pharyngeal swab-based HPV testing and blood based personalized ctDNA sequencing panel testing. Additional control cohorts will include cervical and anal cancer patients as well as cancer-free patients with recently diagnosed oncogenic HPV infections. Using in vivo fluorescence imaging techniques, we will generate fundamental knowledge on renal handling of cell free DNA and determine the impact of chronic kidney disease and other patient, disease and iatrogenic factors on cell free DNA excretion.