The Translational Potential of Cell Free Mutant DNA for Muscle Invasive Bladder Cancer
BAUS ePoster online library. Patel K. 06/30/16; 132017; P11-2
Mr. Keval Patel
Mr. Keval Patel
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Abstract
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P11-2

Introduction: Only 50% of patients with muscle invasive bladder cancer (MIBC) respond to Neoadjuvant Chemotherapy (NAC). Overtreatment of non-responders therefore, represents a major drawback. At present, we are unable to accurately and promptly identify responders. The analysis of tumour-derived mutant cell-free DNA (cfDNA) may identify response promptly due to its short half-life and has hitherto been unreported. For urological cancers, direct shedding of mutant DNA into urine may increase mutant:wild type ratio and more informative than plasma as a non-invasive liquid biopsy.

Methods: Interim analysis was performed on sequential plasma, urine cell-pellet and urine supernatant samples from 8 MIBC patients. DNA was extracted with optimised protocols. Single Nucleotide Variants (SNVs) of multiple genes were assessed by high-throughput Tagged-AMplicon Sequencing, and Copy Number Alterations (CNAs) were analysed using shallow Whole Genome Sequencing (sWGS), based on previous descriptions.

Results: 14 SNVs were detected in 7 patients. When comparing peripheral fluids, SNVs were detected in the plasma 5 times, urine cell-pellet 21 times and urine supernatant 15 times, indicating that for MIBC, SNVs are detected more frequently in urine. CNAs were detected in all tumour samples and were present in the peripheral fluids in 4 of 6 patients analysed to date.

Conclusions: Interim analysis of MIBC patients suggests that urinary cfDNA is more informative than plasma for mutational analysis. Liquid biopsies can provide continual monitoring of tumour burden and mutational profile. Urinary mutant cfDNA analysis could therefore, play an important role in detecting treatment response in patients undergoing NAC for MIBC.

P11-2

Introduction: Only 50% of patients with muscle invasive bladder cancer (MIBC) respond to Neoadjuvant Chemotherapy (NAC). Overtreatment of non-responders therefore, represents a major drawback. At present, we are unable to accurately and promptly identify responders. The analysis of tumour-derived mutant cell-free DNA (cfDNA) may identify response promptly due to its short half-life and has hitherto been unreported. For urological cancers, direct shedding of mutant DNA into urine may increase mutant:wild type ratio and more informative than plasma as a non-invasive liquid biopsy.

Methods: Interim analysis was performed on sequential plasma, urine cell-pellet and urine supernatant samples from 8 MIBC patients. DNA was extracted with optimised protocols. Single Nucleotide Variants (SNVs) of multiple genes were assessed by high-throughput Tagged-AMplicon Sequencing, and Copy Number Alterations (CNAs) were analysed using shallow Whole Genome Sequencing (sWGS), based on previous descriptions.

Results: 14 SNVs were detected in 7 patients. When comparing peripheral fluids, SNVs were detected in the plasma 5 times, urine cell-pellet 21 times and urine supernatant 15 times, indicating that for MIBC, SNVs are detected more frequently in urine. CNAs were detected in all tumour samples and were present in the peripheral fluids in 4 of 6 patients analysed to date.

Conclusions: Interim analysis of MIBC patients suggests that urinary cfDNA is more informative than plasma for mutational analysis. Liquid biopsies can provide continual monitoring of tumour burden and mutational profile. Urinary mutant cfDNA analysis could therefore, play an important role in detecting treatment response in patients undergoing NAC for MIBC.

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