Circulating tumor DNA (ctDNA) has emerged as a promising tool for various clinical applications, including early diagnosis, therapeutic target identification, treatment response monitoring, prognosis evaluation, and minimal residual disease detection. Consequently, ctDNA assays have been incorporated into clinical practice. In this review, we offer an indepth exploration of the clinical implementation of ctDNA assays. Notably, we examined existing evidence related to pre-analytical procedures, analytical components in current technologies, and result interpretation and reporting processes. The primary objective of this guidelines is to provide recommendations for the clinical utilization of ctDNA assays.

Activating mutations in the epidermal growth factor receptor (EGFR) gene, particularly in the tyrosine kinase domain, occur in approximately 20% of non-small cell lung cancer (NSCLC) cases. These mutations, commonly found as deletions in exon 19 or the L858R mutation in exon 21, are crucial targets for EGFR tyrosine kinase inhibitors (TKIs). The third-generation EGFR TKI, osimertinib (TAGRISSO; AstraZeneca, UK), is effective against tumors with the T790M mutation and a liquid biopsy test has been approved by the US Food and Drug Administration as a companion diagnostic for TAGRISSO.This test is now widely implemented in various countries, including South Korea. To ensure high-quality testing, the Korean Association of External Quality Assessment Service launched a liquid biopsy EGFR proficiency testing program in 2017. This study analyzed the results of this program for 2017–2023. The number of participating laboratories increased from three in 2017 to 30 in 2023. All participating laboratories reported results using the Cobas z 480 analyzer (Roche Diagnostics, Germany). The accuracy of the test results was high with 100% correctness in several trials. However, errors were reported in some trials with false positives (e.g., detecting mutations in mutation-free samples) being more common than false negatives. This study evaluated Korean clinical laboratory performance when undertaking liquid biopsies for EGFR mutations. Continuous participation in the external quality assessment program helps laboratories maintain and improve the quality of liquid biopsy EGFR testing, ultimately benefiting patient care by ensuring accurate and reliable mutation detection.

Next-generation sequencing (NGS)-based liquid biopsy using peripheral blood offers a minimally invasive approach to detect tumor-derived circulating tumor DNA (ctDNA). Given the low abundance of ctDNA, accurate analysis is crucial, necessitating external quality assessments.Since 2020, the Korean Association of External Quality Assessment Service has conducted proficiency testing for NGS-based liquid biopsy. This study reviews the proficiency testing results from 2020 to 2023. The program was conducted biannually. Specimens were created by spiking fragmented DNA into fresh frozen plasma to simulate actual clinical samples. The number of target genes reported increased from 5 in 2020 to 17 in 2023. Results were assessed based on concordance with those obtained from targeted NGS panel testing performed before shipping the manufactured specimens.Participating laboratories used various NGS instruments and reagents. The read depth for each genetic variant varied across laboratories, while the reported read percentage of detected variants was generally consistent.Most laboratories accurately reported variants; however, some discrepancies related to variant position descriptions or incorrect reference sequence transcripts were noted. This study evaluates the performance of Korean clinical laboratories in NGS-based liquid biopsy. Continued vigilance in result reporting is necessary, and ongoing external quality assessments can enhance the reliability of NGS-based liquid biopsy testing.

Activating mutations in the epidermal growth factor receptor (EGFR) gene, particularly in the tyrosine kinase domain, occur in approximately 20% of non-small cell lung cancer (NSCLC) cases. These mutations, commonly found as deletions in exon 19 or the L858R mutation in exon 21, are crucial targets for EGFR tyrosine kinase inhibitors (TKIs). The third-generation EGFR TKI, osimertinib (TAGRISSO; AstraZeneca, UK), is effective against tumors with the T790M mutation and a liquid biopsy test has been approved by the US Food and Drug Administration as a companion diagnostic for TAGRISSO.This test is now widely implemented in various countries, including South Korea. To ensure high-quality testing, the Korean Association of External Quality Assessment Service launched a liquid biopsy EGFR proficiency testing program in 2017. This study analyzed the results of this program for 2017–2023. The number of participating laboratories increased from three in 2017 to 30 in 2023. All participating laboratories reported results using the Cobas z 480 analyzer (Roche Diagnostics, Germany). The accuracy of the test results was high with 100% correctness in several trials. However, errors were reported in some trials with false positives (e.g., detecting mutations in mutation-free samples) being more common than false negatives. This study evaluated Korean clinical laboratory performance when undertaking liquid biopsies for EGFR mutations. Continuous participation in the external quality assessment program helps laboratories maintain and improve the quality of liquid biopsy EGFR testing, ultimately benefiting patient care by ensuring accurate and reliable mutation detection.

Next-generation sequencing (NGS)-based liquid biopsy using peripheral blood offers a minimally invasive approach to detect tumor-derived circulating tumor DNA (ctDNA). Given the low abundance of ctDNA, accurate analysis is crucial, necessitating external quality assessments.Since 2020, the Korean Association of External Quality Assessment Service has conducted proficiency testing for NGS-based liquid biopsy. This study reviews the proficiency testing results from 2020 to 2023. The program was conducted biannually. Specimens were created by spiking fragmented DNA into fresh frozen plasma to simulate actual clinical samples. The number of target genes reported increased from 5 in 2020 to 17 in 2023. Results were assessed based on concordance with those obtained from targeted NGS panel testing performed before shipping the manufactured specimens.Participating laboratories used various NGS instruments and reagents. The read depth for each genetic variant varied across laboratories, while the reported read percentage of detected variants was generally consistent.Most laboratories accurately reported variants; however, some discrepancies related to variant position descriptions or incorrect reference sequence transcripts were noted. This study evaluates the performance of Korean clinical laboratories in NGS-based liquid biopsy. Continued vigilance in result reporting is necessary, and ongoing external quality assessments can enhance the reliability of NGS-based liquid biopsy testing.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants. Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines. Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040). Conclusion The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

Activating mutations in the epidermal growth factor receptor (EGFR) gene, particularly in the tyrosine kinase domain, occur in approximately 20% of non-small cell lung cancer (NSCLC) cases. These mutations, commonly found as deletions in exon 19 or the L858R mutation in exon 21, are crucial targets for EGFR tyrosine kinase inhibitors (TKIs). The third-generation EGFR TKI, osimertinib (TAGRISSO; AstraZeneca, UK), is effective against tumors with the T790M mutation and a liquid biopsy test has been approved by the US Food and Drug Administration as a companion diagnostic for TAGRISSO.This test is now widely implemented in various countries, including South Korea. To ensure high-quality testing, the Korean Association of External Quality Assessment Service launched a liquid biopsy EGFR proficiency testing program in 2017. This study analyzed the results of this program for 2017–2023. The number of participating laboratories increased from three in 2017 to 30 in 2023. All participating laboratories reported results using the Cobas z 480 analyzer (Roche Diagnostics, Germany). The accuracy of the test results was high with 100% correctness in several trials. However, errors were reported in some trials with false positives (e.g., detecting mutations in mutation-free samples) being more common than false negatives. This study evaluated Korean clinical laboratory performance when undertaking liquid biopsies for EGFR mutations. Continuous participation in the external quality assessment program helps laboratories maintain and improve the quality of liquid biopsy EGFR testing, ultimately benefiting patient care by ensuring accurate and reliable mutation detection.

Next-generation sequencing (NGS)-based liquid biopsy using peripheral blood offers a minimally invasive approach to detect tumor-derived circulating tumor DNA (ctDNA). Given the low abundance of ctDNA, accurate analysis is crucial, necessitating external quality assessments.Since 2020, the Korean Association of External Quality Assessment Service has conducted proficiency testing for NGS-based liquid biopsy. This study reviews the proficiency testing results from 2020 to 2023. The program was conducted biannually. Specimens were created by spiking fragmented DNA into fresh frozen plasma to simulate actual clinical samples. The number of target genes reported increased from 5 in 2020 to 17 in 2023. Results were assessed based on concordance with those obtained from targeted NGS panel testing performed before shipping the manufactured specimens.Participating laboratories used various NGS instruments and reagents. The read depth for each genetic variant varied across laboratories, while the reported read percentage of detected variants was generally consistent.Most laboratories accurately reported variants; however, some discrepancies related to variant position descriptions or incorrect reference sequence transcripts were noted. This study evaluates the performance of Korean clinical laboratories in NGS-based liquid biopsy. Continued vigilance in result reporting is necessary, and ongoing external quality assessments can enhance the reliability of NGS-based liquid biopsy testing.