Molecular classification and diagnostics of upper urinary tract urothelial carcinoma.

IF 3.8 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS Journal of Proteome Research Pub Date : 2021-06-14 DOI:10.1016/j.ccell.2021.05.008

Yoichi Fujii, Yusuke Sato, Hiromichi Suzuki, Nobuyuki Kakiuchi, Tetsuichi Yoshizato, Andrew T Lenis, Shigekatsu Maekawa, Akira Yokoyama, Yasuhide Takeuchi, Yoshikage Inoue, Yotaro Ochi, Yusuke Shiozawa, Kosuke Aoki, Kenichi Yoshida, Keisuke Kataoka, Masahiro M Nakagawa, Yasuhito Nannya, Hideki Makishima, Jimpei Miyakawa, Taketo Kawai, Teppei Morikawa, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Genta Nagae, Masashi Sanada, Eiji Sugihara, Taka-Aki Sato, Tohru Nakagawa, Masashi Fukayama, Tetsuo Ushiku, Hiroyuki Aburatani, Satoru Miyano, Jonathan A Coleman, Yukio Homma, David B Solit, Haruki Kume, Seishi Ogawa

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引用次数: 56

Abstract

Upper urinary tract urothelial carcinoma (UTUC) is one of the common urothelial cancers. Its molecular pathogenesis, however, is poorly understood, with no useful biomarkers available for accurate diagnosis and molecular classification. Through an integrated genetic study involving 199 UTUC samples, we delineate the landscape of genetic alterations in UTUC enabling genetic/molecular classification. According to the mutational status of TP53, MDM2, RAS, and FGFR3, UTUC is classified into five subtypes having discrete profiles of gene expression, tumor location/histology, and clinical outcome, which is largely recapitulated in an independent UTUC cohort. Sequencing of urine sediment-derived DNA has a high diagnostic value for UTUC with 82.2% sensitivity and 100% specificity. These results provide a solid basis for better diagnosis and management of UTUC.

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上尿路尿路上皮癌的分子分类与诊断。

上尿路尿路上皮癌(UTUC)是常见的尿路上皮癌之一。然而，其分子发病机制尚不清楚，没有有用的生物标志物可用于准确诊断和分子分类。通过一项涉及199个UTUC样本的综合遗传学研究，我们描绘了UTUC遗传改变的景观，从而实现了遗传/分子分类。根据TP53、MDM2、RAS和FGFR3的突变状态，UTUC被分为五种亚型，它们在基因表达、肿瘤位置/组织学和临床结局方面具有离散的特征，这在一个独立的UTUC队列中得到了很大的概括。尿液沉积物来源的DNA测序对UTUC具有很高的诊断价值，敏感性为82.2%，特异性为100%。这些结果为更好地诊断和治疗UTUC提供了坚实的基础。

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来源期刊

Journal of Proteome Research 生物-生化研究方法

CiteScore

9.00

自引率

4.50%

发文量

251

审稿时长

3 months

期刊介绍： Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".