Feasibility of monitoring advanced melanoma patients using cell‐free DNA from plasma |
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| Authors: | Tara C. Gangadhar Samantha L. Savitch Stephanie S. Yee Wei Xu Alexander C. Huang Shannon Harmon David B. Lieberman Devon Soucier Ryan Fan Taylor A. Black Jennifer J. D. Morrissette Neeraj Salathia Jill Waters Shile Zhang Jonathan Toung Paul van Hummelen Jian‐Bing Fan Xiaowei Xu Ravi K. Amaravadi Lynn M. Schuchter Giorgos C. Karakousis Wei‐Ting Hwang Erica L. Carpenter |
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| Affiliation: | 1. Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA;2. Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA;3. Institue for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA;4. Parker Institute of Immunotherapy, University of Pennsylvania, Philadelphia, PA, USA;5. Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA;6. Illumina Inc., San Diego, CA, USA;7. Grail Bio, Redwood City, CA, USA;8. Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA;9. Department of Biostatistics & Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA |
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| Abstract: | To determine the feasibility of liquid biopsy for monitoring of patients with advanced melanoma, cell‐free DNA was extracted from plasma for 25 Stage III/IV patients, most (84.0%) having received previous therapy. DNA concentrations ranged from 0.6 to 390.0 ng/ml (median = 7.8 ng/ml) and were positively correlated with tumor burden as measured by imaging (Spearman rho = 0.5435, p = .0363). Using ultra‐deep sequencing for a 61‐gene panel, one or more mutations were detected in 12 of 25 samples (48.0%), and this proportion did not vary significantly for patients on or off therapy at the time of blood draw (52.9% and 37.5% respectively; p = .673). Sixteen mutations were detected in eight different genes, with the most frequent mutations detected in BRAF, NRAS, and KIT. Allele fractions ranged from 1.1% to 63.2% (median = 29.1%). Among patients with tissue next‐generation sequencing, nine of 11 plasma mutations were also detected in matched tissue, for a concordance of 81.8%. |
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| Keywords: | cell‐free circulating tumor DNA liquid biopsy melanoma precision medicine |
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