Collaborative study from the Bladder Cancer Advocacy Network for the genomic analysis of metastatic urothelial cancer.
Collaborative study from the Bladder Cancer Advocacy Network for the genomic analysis of metastatic urothelial cancer.
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DOI：
10.1038/s41467-022-33980-9
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发表时间：
2022-11-04
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
尿路上皮癌 - 改善患者预后的基因组分析和研究 (NCT02643043)，UC-GENOME，是一项对 218 名转移性尿路上皮癌患者进行的基因组分析和生物样本库研究。在这里，我们报告了 UC-GENOME 的主要结果——接受下一代测序 (NGS) 和治疗方案的受试者比例——并提出了初步的基因组分析和临床相关性。 69.3% 的受试者有潜在的治疗选择，但只有 5.0% 的受试者接受了基于 NGS 的治疗。我们发现与非转移队列相比，TP53E285K 突变频率增加，并确定了与化疗和免疫检查点抑制获益相关的特征，包括：Ba/Sq 和富含基质的亚型、APOBEC 突变特征 (SBS13) 和炎症肿瘤免疫表型。最后，我们推导出一个计算模型，结合了预测免疫检查点抑制剂反应的基因组和临床特征。未来的工作将利用生物样本以及这些基础分析来更好地了解尿路上皮癌生物学。膀胱癌倡导网络建立了 UC-GENOME 研究，旨在创建转移性尿路上皮癌的生物库和数据存储库。在这里，作者首次对 UC-GENOME 中 218 名患者的 DNA 和 RNA 测序数据进行了表征和分析。
Urothelial Cancer - Genomic Analysis to Improve Patient Outcomes and Research (NCT02643043), UC-GENOME, is a genomic analysis and biospecimen repository study in 218 patients with metastatic urothelial carcinoma. Here we report on the primary outcome of the UC-GENOME—the proportion of subjects who received next generation sequencing (NGS) with treatment options—and present the initial genomic analyses and clinical correlates. 69.3% of subjects had potential treatment options, however only 5.0% received therapy based on NGS. We found an increased frequency of TP53E285K mutations as compared to non-metastatic cohorts and identified features associated with benefit to chemotherapy and immune checkpoint inhibition, including: Ba/Sq and Stroma-rich subtypes, APOBEC mutational signature (SBS13), and inflamed tumor immune phenotype. Finally, we derive a computational model incorporating both genomic and clinical features predictive of immune checkpoint inhibitor response. Future work will utilize the biospecimens alongside these foundational analyses toward a better understanding of urothelial carcinoma biology. The Bladder Cancer Advocacy Network established the UC-GENOME study in order to create a biobank and data repository for metastatic urothelial carcinoma. Here, the authors present the first characterization and analysis of DNA and RNA sequencing data from the 218 patients included in the UC-GENOME.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
8.8
作者：
Rose, Tracy L.;Weir, William H.;Kim, William Y.
通讯作者：
Kim, William Y.
影响因子：
8
作者：
Kardos, Jordan;Chai, Shengjie;Vincent, Benjamin G.
通讯作者：
Vincent, Benjamin G.
影响因子：
5.2
作者：
Polano, Maurizio;Chierici, Marco;Toffoli, Giuseppe
通讯作者：
Toffoli, Giuseppe
DOI：
10.1093/bioinformatics/btv408
发表时间：
2015-11-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Gehring JS;Fischer B;Lawrence M;Huber W
通讯作者：
Huber W