Cancer is often described as a disease of the genome, but this underlying biology introduces layers of complexity. Some cancer variants are inherited, whereas others emerge over time. Several are easy to pinpoint, while others hide in complex regions or span large stretches of the genome. And for cancer testing, the real challenge is not just detecting variation, but understanding which signals are meaningful enough to guide interpretation and decision making.
This is where sequencing strategy comes into focus. Whole genome sequencing and targeted panels each offer a different way of looking at cancer, and the choice between them can shape what is discovered, what is missed, and how confidently results can be interpreted.
Whole genome sequencing for comprehensive cancer testing
By definition, whole genome sequencing (WGS) offers the most complete view of the genome. Rather than limiting analysis to a set of predefined genes, paired tumor–normal whole genome sequencing can detect and phase SNVs, structural variants, indels, CNVs, and methylation changes in a single assay.
That breadth matters because cancer biology does not always follow neat boundaries. Structural variants and complex rearrangements are often key drivers of disease, yet they can fall outside the scope of targeted assays. This is especially relevant in rare cancers and hematologic malignancies, where cryptic or novel fusions are relatively common and may be missed by standard approaches. For example, a meaningful portion of pediatric leukemia cases contain these hidden variants, which can directly impact treatment decisions.
As Dr. Midhat Farooqi, leader in pediatric leukemia research, explains –
“Finding structural rearrangements and other genetic abnormalities is important because genetic information has significant impacts on diagnosis, prognosis, and therapy.”
Ultimately, highly accurate long-read sequencing offers a more complete view of the cancer genome, transcriptome, and epigenome that is needed for findings. WGS also reduces the need for fragmented testing. Instead of layering multiple assays to capture different variant types, a single workflow can provide a more unified view. This can improve clarity in rare or unresolved cases and create datasets that remain valuable as new biomarkers emerge.
Targeted panels for focused cancer insights
Alternatively, targeted sequencing takes a more selective approach than WGS by focusing on genes and regions with established clinical relevance. This makes them efficient, scalable, and well-suited for routine testing environments.
Targeted panels are particularly useful when the clinical question is well defined, as is often the case with hereditary cancers. These cancers are driven by inherited variants in known genes, and panels can efficiently assess these regions to support risk evaluation. At the same time, many of these genes sit in repetitive or highly homologous regions, which can make accurate detection challenging depending on the sequencing method.
Panels also fit well into studies built around specific gene sets. Their predictable data output and streamlined analysis pipelines can make them accessible for labs with limited bioinformatics resources.
Where HiFi makes the difference in cancer testing
By providing accurate multiomic sequencing in a single scalable workflow, HiFi technology is uniquely positioned to strengthen both approaches. The extraordinary accuracy and read length at the foundation of the technology allows it to capture complex genomic features while maintaining the confidence needed for clinical research applications.
In WGS, HiFi delivers a comprehensive and integrated view of the cancer genome. It enables accurate detection of phased, structural variants, repeat expansions, gene fusions, and RNA isoforms, all within a single workflow. It also supports 5mC, 5hmC, and 6mA methylation analysis without additional sample preparation, helping connect genetic and epigenetic signals. This multiomic capability is especially valuable in cancers where complexity drives disease biology, such as pediatric tumors, rare cancers, and hematologic malignancies.
Just as importantly, these capabilities help consolidate testing. Instead of running separate assays for different variant classes or adding RNA based methods to confirm fusions, a single HiFi workflow can capture many of these signals together. This reduces the risk of missed variants, preserves samples, and simplifies laboratory workflows while still delivering a complete picture of the genome.
In targeted sequencing, HiFi brings similar advantages to a more focused context. Amplicon sequencing enables deep interrogation of small gene sets with high accuracy. Hybrid capture approaches expand this to larger panels, supporting the detection of structural variants, indels, and variants in difficult regions. PureTarget adds another layer of specificity by offering custom panels with the ability to resolve difficult loci such as tandem repeat expansions and large non-repeat regions.
These advantages are particularly important in hereditary cancer testing, where clinically relevant genes are often located in repetitive or highly homologous regions. HiFi sequencing can resolve these regions more effectively, improving variant detection and reducing ambiguity in results. The result is a targeted approach that retains efficiency while expanding what is actually detectable.
Industry-leading partners for cancer testing
The capabilities of HiFi sequencing for cancer testing are extended through partnerships with industry leaders who develop workflows specifically optimized to bring comprehensive HiFi sequencing to real-world systems.
The SureSelect Cancer CGP panel from Agilent offers a comprehensive genomic profiling solution targeting hundreds of cancer related genes in a flexible hybrid capture workflow. This panel is designed to improve detection of structural variants, indels, and complex regions while integrating smoothly into existing laboratory processes. In particular, its compatibility with established automation systems and familiar workflows helps labs adopt and scale targeted sequencing more seamlessly.
QIAGEN provides the QIAseq xHYB Long Read Hereditary Cancer Panel, which focuses on germline cancer risk assessment. This panel targets dozens of genes with known structural variation and includes full gene coverage across exons, introns, and regulatory regions. The design is optimized for long-read sequencing, enabling more accurate analysis of difficult genomic regions and supporting comprehensive variant characterization in hereditary cancer testing. Variant interpretation is offered through the QIAGEN CLC workbench tool for a true end-to-end solution.
Together, these partners offer accessible entry points into HiFi sequencing for cancer testing, with validated workflows and support that help labs expand their capabilities without adding unnecessary complexity.
The future of cancer testing with HiFi WGS and targeted sequencing
The future of cancer testing is being shaped by technologies that can capture more of the genome with greater clarity. HiFi sequencing is central to that shift, enabling comprehensive sequencing toward the goal of finding clearer, more meaningful answers to inform decision making in cancer research.
If you are thinking about how to bring these approaches into your own work, take a closer look at the cancer genomics brochure, step into the interactive Cancer Breakthroughs experience, or dive into the somatic workflow App note, hybrid capture App brief, or PureTarget custom panels Tech note.
For more information on our partner panels, read through Qiagen’s long-read workflow and listen to our podcast with Agilent for a deep dive on this collaboration.