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번호	년도	제목	저널명	링크
32	2026	Clinical utility of pleural effusion supernatant cell-free DNA genotyping in previously treated patients with advanced non-small-cell lung cancer and disease progression: a multicenter retrospective study Abstract This multicenter retrospective study evaluated the clinical utility of cell-free DNA (cfDNA) fr\|om pleural effusion supernatant in detecting actionable genomic alterations in advanced non-small-cell lung cancer (NSCLC) patients with disease progression after prior therapy. cfDNA next-generation sequencing (NGS) increased the detection of driver mutations compared with standard molecular testing. Specific genomic changes such as MET copy number gain (CNG) and MYC CNG were linked to poorer outcomes, demonstrating that pleural cfDNA genotyping is a valuable tool for guiding personalized treatment strategies in NSCLC. Purpose The study aimed to assess whether pleural effusion supernatant cfDNA sequencing can improve the detection of genomic alterations in patients with advanced NSCLC who have experienced disease progression after prior treatments, and to determine the clinical relevance of these findings in informing subsequent therapy decisions. Materials and Methods -A multicenter retrospective cohort of 95 advanced NSCLC patients with disease progression after at least one line of therapy was analyzed. -Pleural effusion supernatant samples were collected and subjected to cfDNA next-generation sequencing (NGS). -The results were compared to standard molecular testing to determine the frequency of actionable mutations detected. -Associations between specific genomic alterations (e.g., EGFR mutations, MET CNG, MYC CNG) and clinical outcomes such as progression-free survival (PFS) were evaluated. Results -Initial standard molecular testing identified driver mutations in 73.7% of patients, whereas pleural effusion cfDNA NGS increased the detection rate to 85.3%. -Acquired EGFR T790M mutations were detected in a significant proportion of patients after progression on earlier EGFR tyrosine kinase inhibitors, allowing effective subsequent therapy with osimertinib. -MET CNG in patients progressing after first-line osimertinib was associated with a significantly shorter median PFS (12.0 vs. 23.0 months). -In patients progressing after second-line osimertinib, MYC CNG was linked to significantly poorer outcomes. -cfDNA fr\|om pleural effusion revealed driver mutations even when tissue or plasma tests were negative. Conclusions cfDNA obtained fr\|om pleural effusion supernatant is a feasible and informative biomarker source for genomic profiling in NSCLC patients with disease progression. This approach increases the detection of actionable mutations and provides critical insights for personalized treatment, particularly in cases where tissue or plasma genotyping may be inadequate. Clinical utility of pleural effusion supernatant cell-free DNA genotyping in previously treated patients with advanced non-small-cell lung cancer and disease progression: a multicenter retrospective study 링크보기	ESMO Open	링크보기
31	2025	Analytical validation of a hybrid-approach combining tumor-informed and tumor-agnostic bespoke ctDNA panel assay for the sensitive detection of minimal residual disease Abstract This study reports the analytical validation of CancerDetect™, a hybrid ctDNA assay that combines tumor-informed bespoke targets and tumor-agnostic clinically actionable mutations to sensitively detect minimal residual disease (MRD). CancerDetect™ achieved an ultra-sensitive limit of detection of 0.001% with high specificity (99.9%), demonstrating robust performance for MRD detection. Purpose The purpose of this study was to analytically validate a hybrid ctDNA assay (CancerDetect™) designed to detect minimal residual disease (MRD) with higher sensitivity than existing liquid biopsy approaches. The assay integrates both personalized tumor-informed mutation targets and tumor-agnostic hotspot regions to expand the detection space and improve sensitivity beyond conventional fixed-panel methods. Materials and Methods -The CancerDetect™ assay combines large-scale mutation profiling with hybridization capture sequencing, integrating both patient-specific (bespoke) mutations and clinically actionable hotspot mutations across 15 genes. -Reference materials with serially diluted variant allele fractions (VAFs) were prepared to assess the limit of detection (LoD) and limit of blank (LoB). -The assay’s specificity, precision, repeatability, and reproducibility were evaluated using control samples, varying operators, reagents, and interference materials to simulate real-world testing conditions. -Analytical performance metrics were measured using deep targeted sequencing and proprietary error-suppression technology Results -CancerDetect™ achieved a limit of detection (LoD) down to 0.001% ctDNA, indicating ultra-sensitive MRD detection capabilities.-Analytical specificity was 99.9% for bespoke regions, with very low false-positive rates.-The test showed robust precision, repeatability, and reproducibility across operators and reagent lots, confirming consistent performance.-Matrix interference tests (e.g., bilirubin, wash buffer) demonstrated that the assay’s performance was not significantly affected by common plasma components.-The assay’s design ensures both high sensitivity and specificity, enabling reliable differentiation between true tumor signals and background noise. Conclusions This study demonstrates that the CancerDetect™ hybrid ctDNA panel assay provides ultra-sensitive and highly specific detection of minimal residual disease, outperforming conventional approaches. Its combination of tumor-informed and tumor-agnostic targets, along with robust analytical performance, supports its potential utility in clinical MRD monitoring to inform treatment decisions and improve patient outcomes. Analytical validation of a hybrid-approach combining tumor-informed and tumor-agnostic bespoke ctDNA panel assay for the sensitive detection of minimal residual disease 링크보기	PLOS One	링크보기
30	2025	Whole genome DNA methylation patterns in tissue and cfDNA associated with fibrosis reflect the complex signature of MASLD Abstract Whole-genome DNA methylation sequencing (WGMS) of liver tissue and circulating cell-free DNA (cfDNA) in patients with MASLD identified fibrosis-associated methylation patterns in both sample types, along with clear sex-specific and immune-related signals. These results demonstrate the potential of cfDNA-based WGMS as a non-invasive approach for comprehensively monitoring MASLD-related fibrosis. Purpose The study aimed to investigate the relationship between whole-genome DNA methylation (DNAm) patterns and fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) by analyzing both liver tissue and circulating cell-free DNA (cfDNA). Prior research on MASLD methylation was limited to specific CpG sites or tissue only, with little consideration of sex differences. This research sought to address these gaps and explore whether cfDNA methylation profiles could reflect fibrosis-associated changes non-invasively. Materials and Methods Liver tissue and cfDNA samples were collected fr\|om patients with MASLD. Whole-genome methylation sequencing (WGMS) was performed on both sample types. After quality filtering, the data were grouped by sex and sample type. CpG bins showing significant correlation with fibrosis stage using statistical filtering were selected. Pathway analyses were conducted based on genomic locations of significant CpG bins. Additionally, cell type deconvolution was performed to infer cellular contributions to the methylation signal, and comparative analyses between tissue and cfDNA profiles were carried out. Results The WGMS analysis identified overlapping and distinct methylation patterns associated with fibrosis across tissue and cfDNA, and between males and females. Pathway analysis revealed multiple fibrosis-related signaling pathways, including Wnt and Notch signaling, with sex-specific differences. Tissue samples showed immune cell signatures associated with fibrosis. cfDNA analysis reflected increased liver-derived DNA fragments and methylation changes similar to tissue patterns, indicating that cfDNA captures fibrosis-associated alterations. Predictive modeling using cfDNA methylation also showed potential for distinguishing fibrosis severity. Conclusions Whole-genome methylation sequencing reveals complex DNA methylation changes associated with MASLD and fibrosis in both tissue and cfDNA. The findings demonstrate that cfDNA WGMS can capture fibrosis-related epigenetic alterations and holds promise as a non-invasive diagnostic approach for fibrosis in MASLD, potentially enabling blood-based detection and monitoring of disease progression. Whole genome DNA methylation patterns in tissue and cfDNA associated with fibrosis reflect the complex signature of MASLD 링크보기	PLOS One	링크보기
29	2025	Enhanced Detection of Druggable Mutations in Non–Small Cell Lung Cancer Using Targeted Collection of Bronchial Washing Fluid Compared With Plasma and Tumor Tissue Abstract PurposeNext-generation sequencing (NGS) has become the gold standard for the molecular testing of patients with non–small cell lung cancer (NSCLC). This prospective study evaluated the performance of NGS using cell-free tumor DNA (ctDNA) extracted fr\|om bronchial washing fluid (BWF) collected via a targeted washing technique to detect druggable mutations. Materials and Methods All study participants simultaneously underwent NGS using three sample types: (1) BWF, (2) plasma, and (3) tumor tissue collected during bronchoscopy. The full patient set (FPS) included all enrolled patients, whereas the analysis intent group (AIG) included patients who underwent successful NGS across all specimen types (BWF, plasma, and tissue). Results Sixty and 50 patients were included in the FPS and AIG groups, respectively. In FPS, the detection rate of druggable mutations in BWF using NGS was 65%, which was significantly higher than that of plasma (47%) and tissue samples (48%; P 5 .003 and P 5 .002, respectively). In the AIG, the concordance rate for detecting druggable mutations between BWF and tissue samples was 94%. In addition, the detection rate of co-occurring genetic alterations in BWF using NGS was significantly higher than that in plasma samples (92% v 64%, P 5 .001), whereas it was comparable with that in tissue samples (92% v 94%, P 5 1.000). No significant adverse events occurred during the BWF collection. ConclusionsNGS using ctDNA fr\|om BWF obtained through a targeted washing technique is a feasible and reliable method for genomic profiling of NSCLC, providing a promising approach for identifying druggable mutations. Enhanced Detection of Druggable Mutations in Non–Small Cell Lung Cancer Using Targeted Collection of Bronchial Washing Fluid Compared With Plasma and Tumor Tissue 링크보기	JCO Precision Oncology	링크보기
28	2025	Pairwise analysis of plasma cell-free DNA before and after palliative second-line paclitaxel plus ramucirumab treatment in patients with metastatic gastric cancer Abstract Background This study compared plasma cell-free DNA (cfDNA) and tumor tissue DNA (ttDNA) to explore the clinical applicability of cfDNA in patients with metastatic gastric cancer (mGC) receiving palliative second-line paclitaxel + ramucirumab treatment. Methods Targeted sequencing of 106 genes was conducted using germline DNA and cfDNA at baseline (baseline-cfDNA) and progressive disease (PD-cfDNA). The results were compared with those of ttDNA-based cancer panel data. Results Of 76 consecutive patients, 46 (27 males; median age 57.5 [range, 32–73] years) who had all three samples were included. Combined analysis of ttDNA and baseline-cfDNA revealed that TP53 (58.7%) was the most frequently mutated gene, followed by CDH1 (26.1%), KRAS (21.7%), and APC (13.0%). For these genes, the sensitivity and positive predictive value of baseline-cfDNA over ttDNA were 71.8% and 51.9%, respectively. When baseline-cfDNA and PD-cfDNA results were combined, 34 patients (73.9%) were found to have additional mutations compared with ttDNA results alone. PD-cfDNA analysis revealed 14 novel pathogenic mutations in ten patients (21.7%). At baseline, patients with a high circulating tumor DNA fraction concentration showed a significantly shorter progression-free survival (PFS) (P = 0.016) in univariable and multivariable analyses. High maximal variant allele frequency (VAF) (P = 0.022), high sum of VAF (P = 0.028), and high TP53 VAF (P = 0.022) were associated with worse PFS in univariable analysis. Conclusions Although cfDNA alone cannot replace ttDNA entirely, cfDNA analysis revealed additional mutations. Notably, PD-cfDNA analysis revealed novel pathogenic mutations that emerged during treatment. Moreover, the baseline circulating tumor DNA fraction concentration and VAF values were associated with longer PFS. Pairwise analysis of plasma cell-free DNA before and after palliative second-line paclitaxel plus ramucirumab treatment in patients with metastatic gastric cancer 링크보기	Gastric Cancer	링크보기