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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Clinical Application of Targeted Deep Sequencing in Solid-Cancer Patients and Utility for Biomarker-Selected Clinical
Seung Tae Kim1, Kyoung-Mee Kim2,3, Nayoung K D Kim4
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Abstract:
Molecular profiling of actionable mutations in refractory cancer patients has the potential to enable "precision medicine," wherein individualized therapies are guided based on genomic profiling. The molecular-screening program was intended to route participants to different candidate drugs in trials based on clinical-sequencing reports. In this screening program, we used a custom target-enrichment panel consisting of cancer-related genes to interrogate single-nucleotide variants, insertions and deletions, copy number variants, and a subset of gene fusions. From August 2014 through April 2015, 654 patients consented to participate in the program at Samsung Medical Center. Of these patients, 588 passed the quality control process for the 381-gene cancer-panel test, and 418 patients were included in the final analysis as being eligible for any anticancer treatment (127 gastric cancer, 122 colorectal cancer, 62 pancreatic/biliary tract cancer, 67 sarcoma/other cancer, and 40 genitourinary cancer patients). Of the 418 patients, 55 (12%) harbored a biomarker that guided them to a biomarker-selected clinical trial, and 184 (44%) patients harbored at least one genomic alteration that was potentially targetable. This study demonstrated that the panel-based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker-selected clinical trials. Given the expanding list of biomarker-selected trials, the guidance percentage to matched trials is anticipated to increase.
Implications For Practice:
This study demonstrated that the panel-based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker-selected clinical trials. Given the expanding list of biomarker-selected trials, the guidance percentage to matched trials is anticipated to increase.
Insights
Molecular profiling of refractory cancer patients using a gene panel test increased clinical trial enrollment. This precision medicine approach identified actionable genomic alterations, guiding 44% of patients to potentially targetable therapies.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Molecular profiling of actionable mutations in refractory cancer patients can enable precision medicine.
- Individualized therapies can be guided by genomic profiling.
- Molecular screening programs aim to match participants to clinical trials based on sequencing reports.
Purpose of the Study:
- To assess the utility of a custom target-enrichment panel for interrogating various genomic alterations in cancer patients.
- To determine the rate of actionable biomarkers and potentially targetable genomic alterations in a cohort of refractory cancer patients.
- To evaluate the impact of panel-based sequencing on clinical trial enrollment for metastatic cancer patients.
Main Methods:
- A custom 381-gene cancer-panel was used for molecular profiling.
- The panel interrogated single-nucleotide variants, insertions/deletions, copy number variants, and gene fusions.
- 654 patients consented, 588 passed quality control, and 418 were included in the final analysis.
Main Results:
- 55 patients (12%) harbored a biomarker guiding them to a biomarker-selected clinical trial.
- 184 patients (44%) had at least one potentially targetable genomic alteration.
- The panel-based sequencing program increased trial enrollment for metastatic cancer patients.
Conclusions:
- Panel-based molecular profiling is effective in identifying actionable targets for precision medicine in refractory cancer.
- This approach enhances the rate of enrollment in biomarker-selected clinical trials.
- The guidance percentage to matched trials is expected to increase with more biomarker-selected trials available.

