Characterization of metastatic urothelial carcinoma via comprehensive genomic profiling of circulating tumor DNA.
Characterization of metastatic urothelial carcinoma via comprehensive genomic profiling of circulating tumor DNA.
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DOI：
10.1002/cncr.31314
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发表时间：
2018-05-15
期刊：
影响因子：
6.2
通讯作者：
Grivas P
中科院分区：
文献类型：
--
作者：
Agarwal N;Pal SK;Hahn AW;Nussenzveig RH;Pond GR;Gupta SV;Wang J;Bilen MA;Naik G;Ghatalia P;Hoimes CJ;Gopalakrishnan D;Barata PC;Drakaki A;Faltas BM;Kiedrowski LA;Lanman RB;Nagy RJ;Vogelzang NJ;Boucher KM;Vaishampayan UN;Sonpavde G;Grivas P
生物标志物引导的临床试验在转移性尿路上皮癌（mUC）中越来越普遍，但无法获得当代肿瘤组织的患者不符合条件。测序技术的进步使无细胞循环DNA （cfDNA）下一代测序（NGS）在临床中很容易获得。本研究的目的是确定cfDNA NGS检测到的mUC基因组图谱是否与历史肿瘤组织NGS研究相似。第二个目的是确定下路mUC （mLTUC）和上路mUC （mUTUC）之间基因组改变（GAs）的频率是否不同。纳入了来自美国13个学术医疗中心的患者，这些患者在2014年至2017年期间被诊断为mUC，并可获得cfDNA NGS结果。cfDNA分析使用市售平台（guarant360）针对73个基因进行。在369例mUC患者中，294例诊断为mLTUC， 75例诊断为mUTUC。在整个mUC队列中共鉴定出2130例GAs：在mLTUC和mUTUC队列中分别鉴定出1610例和520例。在mLTUC队列中，cfDNA NGS和历史肿瘤组织研究中经常观察到的GAs相似，包括肿瘤蛋白p53 (TP53) (P = 1.000和。（P = 0.058）； （P = 0.058）；（P = 0.058），磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α (PIK3CA) （P = 0.058）。erb-b2受体酪氨酸激酶2 (ERBB2) (P = .565；0.074)和成纤维细胞生长因子受体3 (FGFR3) (P = 0.164和。014年,分别)。在mLTUC和mUTUC患者之间，GAs的发生频率没有显著差异。在没有肿瘤组织的mUC患者中，cfDNA NGS能够在生物标志物驱动的临床试验中识别出与肿瘤组织相似的GAs谱。尽管临床病程更具侵袭性，但mUTUC病例表现出与mLTUC相似的循环肿瘤DNA基因组景观。
Biomarker-guided clinical trials are increasingly common in metastatic urothelial carcinoma (mUC), yet patients for whom contemporary tumor tissue is not available are not eligible. Technological advancements in sequencing have made cell-free circulating DNA (cfDNA) next-generation sequencing (NGS) readily available in the clinic. The objective of the current study was to determine whether the genomic profile of mUC detected by NGS of cfDNA is similar to historical tumor tissue NGS studies. A secondary objective was to determine whether the frequency of genomic alterations (GAs) differed between lower tract mUC (mLTUC) and upper tract mUC (mUTUC). Patients from 13 academic medical centers in the United States who had a diagnosis of mUC between 2014 and 2017 and for whom cfDNA NGS results were available were included. cfDNA profiling was performed using a commercially available platform (Guardant360) targeting 73 genes. Of 369 patients with mUC, 294 were diagnosed with mLTUC and 75 with mUTUC. A total of 2130 GAs were identified in the overall mUC cohort: 1610 and 520, respectively, in the mLTUC and mUTUC cohorts. In the mLTUC cohort, frequently observed GAs were similar between cfDNA NGS and historical tumor tissue studies, including tumor protein p53 (TP53) (P = 1.000 and .115, respectively), AT-rich interaction domain 1A (ARID1A) (P = .058 and .058, respectively), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (P = .058 and .067, respectively), erb-b2 receptor tyrosine kinase 2 (ERBB2) (P = .565 and .074, respectively), and fibroblast growth factor receptor 3 (FGFR3) (P = .164 and .014, respectively). No significant difference was observed with regard to the frequency of GAs between patients with mLTUC and mUTUC. Among patients with mUC for whom no tumor tissue was available, cfDNA NGS was able to identify a similar profile of GAs for biomarker-driven clinical trials compared with tumor tissue. Despite the more aggressive clinical course, cases of mUTUC demonstrated a circulating tumor DNA genomic landscape that was similar to that of mLTUC.
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影响因子：
7.3
作者：
Leow JJ;Chong KT;Chang SL;Bellmunt J
通讯作者：
Bellmunt J
影响因子：
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Janku F;Wheler JJ;Naing A;Stepanek VM;Falchook GS;Fu S;Garrido-Laguna I;Tsimberidou AM;Piha-Paul SA;Moulder SL;Lee JJ;Luthra R;Hong DS;Kurzrock R
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Kurzrock R
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45.3
作者：
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Segal, Neil H.
影响因子：
45.3
作者：
Hussain, Maha H. A.;MacVicar, Gary R.;Smith, David C.
通讯作者：
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影响因子：
4.7
作者：
Herter-Sprie GS;Greulich H;Wong KK
通讯作者：
Wong KK