scholarly journals Circulating Tumor DNA as a Marker for Treatment Response in Metastatic Melanoma Patients Using Next-Generation Sequencing—A Prospective Feasibility Study

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3101
Author(s):  
Marina Berger ◽  
Andrea Thueringer ◽  
Doritt Franz ◽  
Nadia Dandachi ◽  
Emina Talakić ◽  
...  

We prospectively performed a longitudinal analysis of circulating tumor DNA (ctDNA) from 149 plasma samples and CT scans in Stage III and IV metastatic melanoma patients (n = 20) treated with targeted agents or immunotherapy using two custom next-generation sequencing (NGS) Ion AmpliSeq™ HD panels including 60 and 81 amplicons in 18 genes, respectively. Concordance of matching cancer-associated mutations in tissue and plasma was 73.3%. Mutant allele frequency (MAF) levels showed a range from 0.04% to 28.7%, well detectable with NGS technologies utilizing single molecule tagging like the AmpliSeq™ HD workflow. Median followup time of the tissue and/or plasma positive cohort (n = 15) was 24.6 months and median progression-free survival (PFS) was 7.8 months. Higher MAF ≥ 1% at baseline was not significantly associated with a risk of progression (Odds Ratio = 0.15; p = 0.155). Although a trend could be seen, MAF levels did not differ significantly over time between patients with and without a PFS event (p = 0.745). Depending on the cell-free DNA amount, NGS achieved a sensitivity down to 0.1% MAF and allowed for parallel analysis of multiple mutations and previously unknown mutations. Our study indicates that NGS gene panels could be useful for monitoring disease burden during therapy with ctDNA in melanoma patients.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 9077-9077 ◽  
Author(s):  
Erica L. Carpenter ◽  
Stephanie S. Yee ◽  
Devon Soucier ◽  
Jennifer J. Morrissette ◽  
Wei Xu ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2228 ◽  
Author(s):  
Russell J. Diefenbach ◽  
Jenny H. Lee ◽  
Alexander M. Menzies ◽  
Matteo S. Carlino ◽  
Georgina V. Long ◽  
...  

Detection of melanoma-associated mutations using circulating tumor DNA (ctDNA) from plasma is a potential alternative to using genomic DNA from invasive tissue biopsies. In this study, we developed a custom melanoma next-generation sequencing (NGS) panel which includes 123 amplicons in 30 genes covering driver and targetable mutations and alterations associated with treatment resistance. Analysis of a cohort of 74 stage III and IV treatment-naïve melanoma patients revealed that sensitivity of ctDNA detection was influenced by the amount of circulating-free DNA (cfDNA) input and stage of melanoma. At the recommended cfDNA input quantity of 20 ng (available in 28/74 patients), at least one cancer-associated mutation was detected in the ctDNA of 84% of stage IV patients and 47% of stage III patients with a limit of detection for mutant allele frequency (MAF) of 0.2%. This custom melanoma panel showed significant correlation with droplet digital PCR (ddPCR) and provided a more comprehensive melanoma mutation profile. Our custom panel could be further optimized by replacing amplicons spanning the TERT promoter, which did not perform well due to the high GC content. To increase the detection rate to 90% of stage IV melanoma and decrease the sensitivity to 0.1% MAF, we recommend increasing the volume of plasma to 8 mL to achieve minimal recommended cfDNA input and the refinement of poorly performing amplicons. Our panel can also be expanded to include new targetable and treatment resistance mutations to improve the tracking of treatment response and resistance in melanoma patients treated with systemic drug therapies.


2018 ◽  
Vol 144 (11) ◽  
pp. 2167-2175 ◽  
Author(s):  
Ya-Sian Chang ◽  
Hsin-Yuan Fang ◽  
Yao-Ching Hung ◽  
Tao-Wei Ke ◽  
Chieh-Min Chang ◽  
...  

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