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• W2600563024 abstract "BACKGROUND Biopsies from patients with high-risk (HR) non–muscle-invasive urothelial carcinoma (NMIUC), especially flat urothelial carcinoma in situ, frequently contain scant diagnostic material or denuded mucosa only, and this precludes further extensive genomic analysis. This study evaluated the use of next-generation sequencing (NGS) analysis of urine cytology material from patients with HR NMIUC in an attempt to identify genetic alterations that might correlate with clinical features and responses to bacille Calmette-Guérin (BCG) treatment. METHODS Forty-one cytology slides from patients with HR NMIUC treated with intravesical BCG were selected for this study. Histological confirmation was available for all cases. The specimens were subjected to NGS analysis with a customized targeted exome capture assay composed of 341 genes. RESULTS In this cohort, genomic alterations were successfully identified in all cytology samples. Mutations were detected down to a 2% allele frequency and chromosomal rearrangements including copy number alterations and gene fusions were identified. The most frequently altered genes included telomerase reverse transcriptase (TERT), tumor protein 53 (TP53), Erb-B2 receptor tyrosine kinase 2 (ERBB2), and chromatin remodeling genes such as lysine demethylase 6A (KDM6A) and AT-rich interaction domain 1A (ARID1A). For patients with matched tumor tissue, cytology specimens revealed all mutations detected in tissue as well as additional mutations, and this suggested that urine might more effectively capture the full genetic heterogeneity of disease than an individual cystectomy. Alterations in multiple genes correlated with clinical and histopathological features, including responses to BCG treatment, flat architecture versus papillary architecture, and smoking history. CONCLUSIONS Urine specimens can replace tissue as a substrate for NGS analysis of HR NMIUC. Several genomic alterations identified in urine specimens might be associated with histological features and clinical characteristics. Cancer Cytopathol 2017;125:416–26. © 2017 American Cancer Society." @default.
• W2600563024 created "2017-04-07" @default.
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• W2600563024 date "2017-03-24" @default.
• W2600563024 modified "2023-10-10" @default.
• W2600563024 title "Next-generation sequencing of urine specimens: A novel platform for genomic analysis in patients with non-muscle-invasive urothelial carcinoma treated with bacille Calmette-Guérin" @default.
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• W2600563024 doi "https://doi.org/10.1002/cncy.21847" @default.
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