Urine based circulating tumor DNA analysis

摘要 尿液是非泌尿生殖系统患者全身循环肿瘤DNA的未被重视的来源 癌症。根据最近的数据显示，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，我们确定了非转移性hpv阳性的口咽癌。 患者作为一个很好的模型系统来检验基于尿液的经肾DNA分析的潜力。我们的 初步数据显示，我们新开发的基于尿液的HPV检测可能具有生物标志物的性能 与基于血液的HPV检测相比，这是有利的。 这项应用的具体目标是确定尿液是非人类乳头瘤病毒DNA的合适来源 转移性HPV阳性口咽癌患者，家庭尿液分子检测是可行的 对这些病人来说。具体地说，我们将比较治疗前尿液HPV的敏感性和特异性。 一组新诊断的非转移性口咽癌的组织金标准检测 病人。尿液HPV检测的复发检测提前时间将与临床常规护理进行比较 治疗意向治疗后的同一队列。控制措施将包括血液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。利用活体荧光成像技术，我们将产生基本的 了解肾脏处理游离DNA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.