通过对循环肿瘤 DNA 的全面基因组分析来鉴定转移性尿路上皮癌。
Characterization of metastatic urothelial carcinoma via comprehensive genomic profiling of circulating tumor DNA.
机构信息
Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California.
出版信息
Cancer. 2018 May 15;124(10):2115-2124. doi: 10.1002/cncr.31314. Epub 2018 Mar 8.
BACKGROUND
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).
METHODS
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.
RESULTS
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.
CONCLUSIONS
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. Cancer 2018;124:2115-24. © 2018 American Cancer Society.
背景
生物标志物指导的临床试验在转移性尿路上皮癌（mUC）中越来越常见，但对于没有当代肿瘤组织的患者则没有资格参加。测序技术的进步使得 cfDNA 下一代测序（NGS）在临床上很容易获得。本研究的目的是确定通过 cfDNA NGS 检测到的 mUC 的基因组谱是否与历史肿瘤组织 NGS 研究相似。次要目的是确定下尿路 mUC（mLTUC）和上尿路 mUC（mUTUC）之间的基因组改变（GA）频率是否不同。
方法
纳入了 2014 年至 2017 年间在美国 13 家学术医疗中心诊断为 mUC 且有 cfDNA NGS 结果的患者。使用商业上可用的平台（Guardant360）对 cfDNA 进行分析，该平台靶向 73 个基因。
结果
在 369 例 mUC 患者中，294 例诊断为 mLTUC，75 例诊断为 mUTUC。在整个 mUC 队列中发现了 2130 个 GA：分别在 mLTUC 和 mUTUC 队列中发现了 1610 个和 520 个。在 mLTUC 队列中，cfDNA NGS 和历史肿瘤组织研究中经常观察到的 GA 相似，包括肿瘤蛋白 p53（TP53）（P=1.000 和.115，分别），富含 AT 的相互作用域 1A（ARID1A）（P=.058 和.058，分别），磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚单位α（PIK3CA）（P=.058 和.067，分别），erb-b2 受体酪氨酸激酶 2（ERBB2）（P=.565 和.074，分别）和成纤维细胞生长因子受体 3（FGFR3）（P=.164 和.014，分别）。mLTUC 和 mUTUC 患者的 GA 频率无显著差异。
结论
对于没有肿瘤组织的 mUC 患者，cfDNA NGS 能够识别出与肿瘤组织相比，用于生物标志物驱动的临床试验的相似 GA 谱。尽管临床病程更为严重，但 mUTUC 的病例显示出与 mLTUC 相似的循环肿瘤 DNA 基因组图谱。癌症 2018;124:2115-24。©2018 美国癌症协会。
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