Comprehensive Tumor Profiling Using NGS:
Precision Oncology, Liquid Biopsy and Clinical Decision Support
Key Takeaways
Summary
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NGS Transforming Precision Oncology
Advances in next-generation sequencing (NGS) are transforming precision oncology by enabling comprehensive tumor profiling, liquid biopsy analysis, and data-driven clinical decisions, supporting faster diagnostics and more personalized cancer treatment. Molecular oncology is undergoing a fundamental transformation. Advances in next-generation sequencing (NGS), integrated bioinformatics, and clinically validated biomarker interpretation are enabling oncologists to move beyond single gene testing towards truly comprehensive, data-driven treatment selection. During a recent Genomics Unlocked webinar, experts from OncoDNA, MGI, and Sistemas Genómicos discussed how integrated NGS workflows are transforming routine cancer diagnostics – shifting from sequential single-gene testing toward comprehensive multi-gene analysis in a single assay.
Historically, treatment selection relied on stepwise testing using methods such as immunohistochemistry (IHC), PCR, and qPCR, where each result guided the next biomarker to evaluate. Today, NGS enables simultaneous analysis of multiple clinically relevant genes, supporting faster therapeutic decisions while also enabling non-invasive monitoring through liquid biopsy and molecular surveillance. This article highlights the key insights from that discussion.
Moving Beyond Single-Gene Testing in Oncology
Modern oncology presents unique diagnostic challenges: tumor heterogeneity, limited and degraded FFPE material, increasing biomarker complexity, and the urgent need for fast, actionable results for rapid therapeutic decisions. Traditional single-gene or small-panel assays struggle to meet these demands. NGS has become the preferred technology for precision oncology because it enables:
- Simultaneous detection of mutations, CNVs, and gene fusions
- Assessment of complex genomic signatures such as TMB, MSI, HRD and LOH
- Scalable testing from small laboratories to high-throughput reference centres
- Seamless integration with clinical interpretation and reporting platforms
- As highlighted during the webinar, this shift represents a move toward standardized, data-driven oncology
Engineered for Clinical Oncology: The Role of MGI Sequencing
High-complexity oncology panels require more than sequencing throughput. Clinical laboratories must also ensure data stability, uniform coverage, and reproducibility across challenging samples such as FFPE tissue and low-input DNA. MGI’s sequencing platforms including the G99, G400, T1+, and T7, are designed to support these requirements across mid- and high-throughput laboratory environments. At the core of these systems is DNA nanoball (DNB) sequencing technology, which minimizes several common sequencing artifacts, including:
- PCR duplicates
- Index hopping
- Error propagation
DNB sequencing uses circularized library fragments and rolling circle replication to generate highly uniform DNA nanoballs prior to sequencing, avoiding PCR amplification directly on the flow cell and reducing amplification bias. For oncology applications, particularly those involving FFPE tissue or low-input DNA, this translates into:
- More uniform genome coverage
- More robust copy number variant (CNV) detection
- Greater sensitivity for low-frequency variants
These performance characteristics are critical for accurate tumor profiling, where uneven amplification or technical noise can directly influence therapeutic interpretation. Integrated workflows that automate steps such as library conversion, DNB generation, and flow cell loading further reduce operator variability, supporting consistent performance in routine clinical laboratory settings.
OncoDeep™: Broad Tumor Profiling
Comprehensive tissue-based profiling within a single, unified sequencing run.
- ✓ Targeted DNA Content: Includes comprehensive profiling of 638 genes analyzed directly at the DNA level.
- ✓ Transcriptome Fusion Panel: Evaluates 22 highly targeted genes at the RNA level specifically for actionable fusion detection.
- ✓ Pan-Cancer Signatures: Simultaneous detection of SNVs, CNVs, gene fusions, alongside vital signatures including LOH, MSI, HRD, and TMB.
- ✓ Enhanced Region Coverage: Features optimized hybrid capture chemistry for historically challenging genomic regions like the TERT promoter.
- ✓ Scalable Flow Cell Delivery: Supports cost-efficient batching of up to 96 samples per run on the G400, or scalable lower-volume lanes via the G99 platform.
Expanding into Liquid Biopsy: OncoSelect™
Non-invasive circulating tumor DNA (ctDNA) analysis for longitudinal care.
- ✓ Clinically Mainmapped Panel: Screens 74 highly relevant oncological genes frequently associated with active treatment decisions.
- ✓ UMI Error Correction: Utilizes Unique Molecular Identifiers (UMIs) to flawlessly filter out background polymerase artifacts and sequencing noise.
- ✓ Ultra-Deep NGS Topography: Achieves an average depth of ~20,000× raw coverage to isolate low-frequency mutant variant alleles.
- ✓ Variant Targeting Scope: Isolates trace somatic SNVs, target rearrangements/fusions, homologous recombination repair (HRR) genes, and TERT alterations.
- ✓ Longitudinal Surveillance: Purpose-built for sensitive, non-invasive therapeutic monitoring, secondary therapy selection, and Minimal Residual Disease (MRD) applications.
Real-World Validation: Experience from Sistemas Genómicos
Sistemas Genómicos, a leading Spanish reference laboratory with over 25 years of experience in genetic diagnostics, presented validation data supporting the integrated MGI/OncoDNA workflow. A total of 90 samples (54 clinical and 36 reference) were analysed. Libraries previously sequenced on alternative platforms were re-sequenced on the G400 to enable direct comparison. Key findings included:
- Optimal performance at DNA inputs of 30–100 ng
- Reduced performance at very low input (6 ng), consistent with limitations observed across platforms
- 100% concordance for MSI and HRD
- Greater than 90% concordance for TMB
These results demonstrated equivalent analytical performance while supporting cost-efficient large-panel oncology testing
Bioinformatics Designed for Clinical Decision Support
Comprehensive tumor profiling requires robust analytical and interpretation frameworks capable of translating complex sequencing data into clinically meaningful insights. OncoKDM, OncoDNA’s cloud-based platform, provides structured visualization and clinical interpretation of sequencing results. Detected genomic alterations are integrated with curated oncology knowledge to support evidence-based treatment decisions. Key capabilities of OncoKDM include:
- Sample-level quality control metrics
- Variant and copy number visualization
- Fusion analysis display
- Calculation and reporting of genomic signatures (e.g., TMB, MSI, HRD)
- Evidence-linked therapy and clinical trial associations
- Downloadable data files (e.g., BAM, VCF, coverage reports)
To further support clinical decision-making, users can apply virtual panels to focus on specific gene sets or clinical contexts, allowing interpretation of the same sequencing dataset without requiring additional wet-lab experiments. The platform also provides access to ongoing clinical trial information, enabling clinicians to identify relevant trial opportunities associated with detected genomic alterations. By centralizing interpretation and reporting within a validated framework, laboratories can streamline analysis workflows while maintaining analytical transparency and traceability.
Frequently Asked Questions
1. What does this integrated oncology workflow enable?
It enables laboratories to perform comprehensive tumor profiling, combining broad biomarker detection, high-accuracy sequencing, and structured clinical interpretation within a single, streamlined workflow.
2. What types of cancer biomarkers can be analyzed?
The workflow supports robust detection of single nucleotide variants (SNVs), copy number variants (CNVs), structural gene fusions, and vital pan-cancer genomic signatures such as Tumor Mutational Burden (TMB), Microsatellite Instability (MSI), Homologous Recombination Deficiency (HRD), and Loss of Heterozygosity (LOH).
3. Why is MGI sequencing used for oncology testing?
MGI's proprietary DNA Nanoball (DNB) sequencing technology dramatically improves coverage uniformity and eliminates PCR duplication artifacts. This ensures highly sensitive and accurate variant calling in notoriously challenging samples like formal-fixed paraffin-embedded (FFPE) tissue and low-input circulating tumor DNA (ctDNA).
4. How are sequencing results translated into treatment recommendations?
Raw sequencing data is seamlessly processed and visualized through OncoDNA’s cloud-based OncoKDM platform. The system programmatically cross-references detected alterations with active clinical trials, globally approved targeted therapies, and curated clinical evidence to generate actionable reports.
5. Can this workflow be implemented in routine clinical laboratories?
Yes. This integrated workflow has been independently validated using real-world clinical samples by reference laboratories and is optimized for scalable, cost-efficient deployment across both mid-volume clinical setups and high-throughput molecular pathology centers.
Toward Longitudinal, Data-Driven Oncology
Looking ahead, speakers highlighted a clear evolution in cancer diagnostics. Oncology testing is evolving beyond static tumor profiling toward integrated, longitudinal molecular strategies that include:
- Expansion toward whole exome based tumor profiling
- Larger RNA and liquid biopsy panels exceeding 400 genes
- Tumor-informed minimal residual disease (MRD) monitoring
- Cohort-level analytics through oncology data intelligence platforms
- Greater automation across sequencing and library preparation
Together, these developments signal a shift from isolated genomic snapshots to continuous, data-driven oncology management. As demonstrated during this webinar, integrating high-accuracy sequencing platforms from MGI with OncoDNA’s assay and interpretation framework validated in routine laboratory practice by Sistemas Genómicos, supports scalable, clinically actionable precision oncology.
Published 21 June 2026
