Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention.
Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention.
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DOI：
10.3390/jcm11195827
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发表时间：
2022-09-30
影响因子：
3.9
通讯作者：
Levin TG
中科院分区：
文献类型：
--
作者：
Bicocca VT;Phillips KG;Fischer DS;Caruso VM;Goudarzi M;Garcia-Ransom M;Lentz PS;MacBride AR;Jensen BW;Mazzarella BC;Koppie T;Korkola JE;Gray JW;Levin TG
尿路上皮癌(UC)的临床护理标准依赖于性能不佳的侵入性手术。为了加强UC的治疗，我们开发了一种尿液综合基因组图谱(UCGP)测试，UroAmplity，它测量存在于尿液中的肿瘤DNA突变。在这项研究中，我们使用参考标准对技术敏感性和阳性预测值(PPV)进行了盲法前瞻性验证，发现当等位基因频率为1%时，突变检测的敏感性为97.4%，阳性预测值(PPV)为80.4%。然后，我们前瞻性地比较了尿液提取的DNA与匹配的肿瘤组织的突变情况，以验证临床表现。在这里，我们发现在尿液中观察到肿瘤单核苷酸变异，中位符合率为91.7%，uCGP显示出不同的基因组损伤模式，在低级别和高级别疾病中丰富。最后，我们回顾了纵向病例研究，以量化保留膀胱治疗后的残留疾病，发现uCGP在接受保留膀胱治疗的患者中检测到残留疾病，并预测复发和疾病进展。这些发现证明了UroAmplity平台在疾病的每个阶段：诊断、治疗和监测--可靠地识别和跟踪与UC相关的突变的潜力。多个案例研究证明了患者风险分类对指导手术和治疗干预的有效性。
The clinical standard of care for urothelial carcinoma (UC) relies on invasive procedures with suboptimal performance. To enhance UC treatment, we developed a urinary comprehensive genomic profiling (uCGP) test, UroAmplitude, that measures mutations from tumor DNA present in urine. In this study, we performed a blinded, prospective validation of technical sensitivity and positive predictive value (PPV) using reference standards, and found at 1% allele frequency, mutation detection performs at 97.4% sensitivity and 80.4% PPV. We then prospectively compared the mutation profiles of urine-extracted DNA to those of matched tumor tissue to validate clinical performance. Here, we found tumor single-nucleotide variants were observed in the urine with a median concordance of 91.7% and uCGP revealed distinct patterns of genomic lesions enriched in low- and high-grade disease. Finally, we retrospectively explored longitudinal case studies to quantify residual disease following bladder-sparing treatments, and found uCGP detected residual disease in patients receiving bladder-sparing treatment and predicted recurrence and disease progression. These findings demonstrate the potential of the UroAmplitude platform to reliably identify and track mutations associated with UC at each stage of disease: diagnosis, treatment, and surveillance. Multiple case studies demonstrate utility for patient risk classification to guide both surgical and therapeutic interventions.
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DOI：
10.6004/jnccn.2018.0072
发表时间：
2018-09-01
影响因子：
13.4
作者：
Flaig, Thomas W.;Spiess, Philippe E.;Gurski, Lisa A.
通讯作者：
Gurski, Lisa A.
影响因子：
4
作者：
Goodison, Steve;Rosser, Charles J.;Urquidi, Virginia
通讯作者：
Urquidi, Virginia
影响因子：
4.5
作者：
Kamat, Ashish M.;Karam, Jose A.;Dinney, Colin P.
通讯作者：
Dinney, Colin P.
Stard 2015：用于报告诊断准确性研究的基本项目的更新列表。
DOI：
10.1136/bmj.h5527
发表时间：
2015-10-28
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Bossuyt PM;Reitsma JB;Bruns DE;Gatsonis CA;Glasziou PP;Irwig L;Lijmer JG;Moher D;Rennie D;de Vet HC;Kressel HY;Rifai N;Golub RM;Altman DG;Hooft L;Korevaar DA;Cohen JF;STARD Group
通讯作者：
STARD Group
影响因子：
64.8
作者：
Abbosh C;Birkbak NJ;Wilson GA;Jamal-Hanjani M;Constantin T;Salari R;Le Quesne J;Moore DA;Veeriah S;Rosenthal R;Marafioti T;Kirkizlar E;Watkins TBK;McGranahan N;Ward S;Martinson L;Riley J;Fraioli F;Al Bakir M;Grönroos E;Zambrana F;Endozo R;Bi WL;Fennessy FM;Sponer N;Johnson D;Laycock J;Shafi S;Czyzewska-Khan J;Rowan A;Chambers T;Matthews N;Turajlic S;Hiley C;Lee SM;Forster MD;Ahmad T;Falzon M;Borg E;Lawrence D;Hayward M;Kolvekar S;Panagiotopoulos N;Janes SM;Thakrar R;Ahmed A;Blackhall F;Summers Y;Hafez D;Naik A;Ganguly A;Kareht S;Shah R;Joseph L;Marie Quinn A;Crosbie PA;Naidu B;Middleton G;Langman G;Trotter S;Nicolson M;Remmen H;Kerr K;Chetty M;Gomersall L;Fennell DA;Nakas A;Rathinam S;Anand G;Khan S;Russell P;Ezhil V;Ismail B;Irvin-Sellers M;Prakash V;Lester JF;Kornaszewska M;Attanoos R;Adams H;Davies H;Oukrif D;Akarca AU;Hartley JA;Lowe HL;Lock S;Iles N;Bell H;Ngai Y;Elgar G;Szallasi Z;Schwarz RF;Herrero J;Stewart A;Quezada SA;Peggs KS;Van Loo P;Dive C;Lin CJ;Rabinowitz M;Aerts HJWL;Hackshaw A;Shaw JA;Zimmermann BG;TRACERx consortium;PEACE consortium;Swanton C
通讯作者：
Swanton C