COMMON SOMATIC MUTATIONS IN UROTHELIAL BLADDER CANCER: FREQUENCY ACROSS GRADES & STAGES, PROGNOSTIC VALUE, AND DETECTION IN URINARY CELL PELLET AND CELL-FREE DNA
BAUS ePoster online library. Ward D. Jun 24, 2019; 259507; P2-3
Dr. Douglas Ward
Dr. Douglas Ward
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Abstract
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Background: Urothelial bladder cancer (UBC) associated genomic alterations can be detected in urinary DNA and may represent clinically-useful biomarkers.
Objective: To develop a panel of somatic mutations (SMs) present in the majority of UBCs and to define their frequency across grades and stages, their prognostic utility and their ability to identify UBC from urinary cell pellet (cp)DNA and urinary cell-free (cf)DNA.
Design, Setting & Participants: A panel of SMs was validated by targeted deep-sequencing of tumour DNA from 956 UBC patients. Amplicon and capture-based targeted sequencing measured mutant allele frequencies (MAFs) of SMs in 314 urine cpDNAs and 153 urine cfDNAs.
Outcome Measurements & Statistical Analysis: The association of SMs with grade, stage, and clinical outcomes were investigated by univariate and multivariate Cox models. Concordance between SMs detected in tumour tissue and cpDNA and cfDNA was assessed.
Results & Limitations: The panel comprised SMs in 23 genes, with 92.3-100% of UBCs of all grades and stages harbouring ≥1 SM. RAS mutations were associated with better overall survival (p=0.04). MAFs in urinary cfDNA and cpDNA were highly correlated. Using a capture-based approach, >94% of tumour SMs were detected in both cp and cfDNA; cpDNA yields were 10-fold higher than for cfDNA.
CONCLUSIONS:
SMs can be reliably detected in both urinary cpDNA and cfDNA and could be used to non-invasively diagnose UBCs whilst also providing additional prognostic information. Capture-based approaches offer increased sensitivity for both cpDNA and cfDNA. cfDNA may be useful to corroborate cpDNA results or if cpDNA yields are insufficient.
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