Molecular characterisation of bladder cancer mutations using plasma cell-free DNA through chemotherapy and radical cystectomy
Author(s):
Dr Pramit Khetrapal
,
Dr Pramit Khetrapal
Affiliations:
Dr Yien Ning Sophia Wong
,
Dr Yien Ning Sophia Wong
Affiliations:
Mr Wei Shen Tan
,
Mr Wei Shen Tan
Affiliations:
Mr Simon Rodney
,
Mr Simon Rodney
Affiliations:
Mr Benjamin Lamb
,
Mr Benjamin Lamb
Affiliations:
Mr Ashwin Sridhar
,
Mr Ashwin Sridhar
Affiliations:
Mr Tim Briggs
,
Mr Tim Briggs
Affiliations:
Prof John Kelly
,
Prof John Kelly
Affiliations:
Dr Andrew Feber
Dr Andrew Feber
Affiliations:
BAUS ePoster online library. Khetrapal P. 06/26/17; 177338; P1-10
Dr. Pramit Khetrapal
Dr. Pramit Khetrapal
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Abstract
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Introduction: Tracking genomic alterations in cell-free DNA (cfDNA) is a novel technique with potential to monitor treatment response in patients with cancer. Identifying truncal mutations within a heterogeneous tumour requires an individualised or multi-target approach to monitor response. The aim of this study is to test the feasibility to detect and monitor somatic mutations in cfDNA of patients with BC.

Methods: 10 patients with metastatic BC, and 20 patients with muscle-invasive BC undergoing cystectomy were included. Patients with metastatic BC received at least two cycles of gemcitabine and cisplatin chemotherapy. Blood (10mls) was collected in EDTA tubes at baseline, and before each cycle of chemotherapy for the metastatic cohort, and 12 weeks after surgery for the cystectomy cohort. cfDNA was extracted from plasma using the QIAamp Circulating Nucleic Acid Kit. Targeted amplification, using dual-indexed primers, followed by next generation sequencing (NGS) was performed using a panel of known (TERT, FGFR3, PIKC3, HRAS) and novel BC mutations. Changes in the cfDNA mutation burden were related to cross-sectional imaging with response measured using the RECIST criteria.

Results: Baseline DNA quantity, mean 77.5 and IQR 10.9-72.7 (Qubit), did not correlate with disease burden, subsequent chemotherapy or response. The mutation profile varied between patients, with at least one mutation detectable in all patients. Dynamic changes in the mutational burden during chemotherapy were evident in several patients. In some patients with lymph node-positive disease, mutations were detectable in post-cystectomy samples.

Conclusion: Mutation analysis of cfDNA is feasible for the non-invasive realtime assessment of tumour burden.
Introduction: Tracking genomic alterations in cell-free DNA (cfDNA) is a novel technique with potential to monitor treatment response in patients with cancer. Identifying truncal mutations within a heterogeneous tumour requires an individualised or multi-target approach to monitor response. The aim of this study is to test the feasibility to detect and monitor somatic mutations in cfDNA of patients with BC.

Methods: 10 patients with metastatic BC, and 20 patients with muscle-invasive BC undergoing cystectomy were included. Patients with metastatic BC received at least two cycles of gemcitabine and cisplatin chemotherapy. Blood (10mls) was collected in EDTA tubes at baseline, and before each cycle of chemotherapy for the metastatic cohort, and 12 weeks after surgery for the cystectomy cohort. cfDNA was extracted from plasma using the QIAamp Circulating Nucleic Acid Kit. Targeted amplification, using dual-indexed primers, followed by next generation sequencing (NGS) was performed using a panel of known (TERT, FGFR3, PIKC3, HRAS) and novel BC mutations. Changes in the cfDNA mutation burden were related to cross-sectional imaging with response measured using the RECIST criteria.

Results: Baseline DNA quantity, mean 77.5 and IQR 10.9-72.7 (Qubit), did not correlate with disease burden, subsequent chemotherapy or response. The mutation profile varied between patients, with at least one mutation detectable in all patients. Dynamic changes in the mutational burden during chemotherapy were evident in several patients. In some patients with lymph node-positive disease, mutations were detectable in post-cystectomy samples.

Conclusion: Mutation analysis of cfDNA is feasible for the non-invasive realtime assessment of tumour burden.
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