Togneri Fiona S, Ward Douglas G, Foster Joseph M, Devall Adam J, Wojtowicz Paula, Alyas Sofia, Vasques Fabiana Ramos, Oumie Assa, James Nicholas D, Cheng K K, Zeegers Maurice P, Deshmukh Nayneeta, O'Sullivan Brendan, Taniere Philippe, Spink Karen G, McMullan Dominic J, Griffiths Mike, Bryan Richard T
West Midland Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
Institute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Eur J Hum Genet. 2016 Aug;24(8):1167-74. doi: 10.1038/ejhg.2015.281. Epub 2016 Jan 13.
Urothelial bladder cancers (UBCs) have heterogeneous clinical characteristics that are mirrored in their diverse genomic profiles. Genomic profiling of UBCs has the potential to benefit routine clinical practice by providing prognostic utility above and beyond conventional clinicopathological factors, and allowing for prediction and surveillance of treatment responses. Urinary DNAs representative of the tumour genome provide a promising resource as a liquid biopsy for non-invasive genomic profiling of UBCs. We compared the genomic profiles of urinary cellular DNA and cell-free DNA (cfDNA) from the urine with matched diagnostic formalin-fixed paraffin-embedded tumour DNAs for 23 well-characterised UBC patients. Our data show urinary DNAs to be highly representative of patient tumours, allowing for detection of recurrent clinically actionable genomic aberrations. Furthermore, a greater aberrant load (indicative of tumour genome) was observed in cfDNA over cellular DNA (P<0.001), resulting in a higher analytical sensitivity for detection of clinically actionable genomic aberrations (P<0.04) when using cfDNA. Thus, cfDNA extracted from the urine of UBC patients has a higher tumour genome burden and allows greater detection of key genomic biomarkers (90%) than cellular DNA from urine (61%) and provides a promising resource for robust whole-genome tumour profiling of UBC with potential to influence clinical decisions without invasive patient interventions.
尿路上皮膀胱癌（UBC）具有异质性临床特征，这在其多样的基因组图谱中得以体现。UBC的基因组分析有潜力通过提供超越传统临床病理因素的预后效用，并实现对治疗反应的预测和监测，从而使常规临床实践受益。代表肿瘤基因组的尿液DNA作为UBC非侵入性基因组分析的液体活检提供了一种有前景的资源。我们比较了23例特征明确的UBC患者尿液中尿细胞DNA和游离DNA（cfDNA）的基因组图谱与匹配的诊断性福尔马林固定石蜡包埋肿瘤DNA。我们的数据表明，尿液DNA高度代表患者肿瘤，能够检测出复发性的具有临床可操作性的基因组畸变。此外，与细胞DNA相比，cfDNA中观察到更高的畸变负荷（指示肿瘤基因组）（P<0.001），这使得在使用cfDNA时检测具有临床可操作性的基因组畸变的分析灵敏度更高（P<0.04）。因此，从UBC患者尿液中提取的cfDNA具有更高的肿瘤基因组负荷，与尿液中的细胞DNA（61%）相比，能够检测到更多的关键基因组生物标志物（90%），并为UBC强大的全基因组肿瘤分析提供了一种有前景的资源，有可能在不进行侵入性患者干预的情况下影响临床决策。
