Gene Solutions today announced the publication of a peer-reviewed study using the K-4CARE assay in Cancer Medicine entitled “Tumor Genomic and Transcriptomic Analysis Integrated with Liquid Biopsy ctDNA Monitoring: Analytical Validation and Clinical Insights”. The work demonstrates how combining comprehensive tumor DNA and mRNA profiling with serial circulating tumor DNA (ctDNA) monitoring can reveal clinically actionable insights that DNA-only or tissue-only approaches may miss, and enable more precise tracking of treatment response over time.
Led by Nam H. B. Tran, along with colleagues and esteemed oncologists across leading cancer centers in collaboration with Gene Solutions, the study analyzed tissue samples spanning 12 cancer types. The team performed targeted DNA sequencing using a 504-gene High-Density Probe (HDP) panel, alongside shallow whole-genome sequencing (sWGS) to enhance genomic profiling. They also conducted transcriptomic (mRNA) profiling to improve detection of MET exon 14 skipping and gene fusions, as well as to predict tissue of origin (TOO) in Cancer of Unknown Primary (CUP) cases using an AI model (OriCUP), trained on 9,889 samples and independently validated on 731 samples.
In a cohort of 55 metastatic lung cancer patients, the researchers integrated liquid biopsy ctDNA with FFPE tissue profiling to assess clinical significance. This innovative approach expanded the detection of actionable mutations and improved ctDNA detection sensitivity. Furthermore, longitudinal ctDNA monitoring revealed that treatment response was strongly associated with progression-free survival (PFS).
Key Findings and Clinical Impacts:
- Superior CNV sensitivity with HDP panel design: DNA sequencing using high density probes provided higher sensitivity than standard panel designs for detecting copy number variations at chromosome, gene, and exon levels. Example BRCA1/2 exon-level large genomic rearrangement (LGR) detection improved sensitivity up to 100%, enabling 2–3% more patients to qualify for BRCA-targeted therapies (1,2).
- mRNA profiling achieved 100% sensitivity for fusion detection: In fusion-positive reference samples, mRNA profiling captured all fusion variants, while DNA profiling detected only 80%, thereby maximizing access to gene fusion-targeted therapies.
- Accurate tissue‑of‑origin prediction: The OriCUP model achieved 87.7% accuracy for primary tumors and 81.4% accuracy for metastatic, supporting more effective site-specific treatment strategies.
- ctDNA dynamics correlate with clinical outcome: Patients experiencing >50% ctDNA decrease from baseline (“molecular responders”) had significantly longer PFS than molecular non‑responders. The 12-month PFS rate was ~3-fold higher in molecular responders vs non-responders (95.5% vs 31.7%) (HR = 9.42; 95% CI: 3.33–26.67; p < 0.0001).
- Integrated LB-ctDNA profiling increased actionable mutations and ctDNA detection rates: LB-ctDNA identified an additional 11.5% tumor-agnostic actionable and resistance mutations.
Read the full study summary: Click here
Open access article in Cancer Medicine: https://doi.org/10.1002/cam4.71465
About K-4CARE
K-4CARE is designed to support complex and advanced cases through comprehensive molecular characterization and follow-up across multiple clinical scenarios. The assay integrates a 504 gene DNA panel and 19,435 RNA targets for comprehensive profiling, combined with ctDNA monitoring:
- Comprehensive DNA (genomic profiling) and mRNA (transcriptomic profiling) provides immune biomarkers, actionable and resistance mutations, germline findings, HRD/HRR‑related assessment, prognostic/diagnostic insights (chromosomes, oncovirus), and tissue‑of‑origin prediction for CUP cases.
- ctDNA–MRD monitoring tracks up to 10 personalized mutations, 1,124 hotspot mutations, viral DNA (HPV, EBV), and genomewide features (CNA and fragmentomics) with a limit of detection (LOD) of 0.01%.
References:
- Thaddeus Judkins B et al. Cancer (2012)
- Do-Hoon Kim et al. BMC Medical Genetics (2017)
