In a webinar supported by Thermo Fisher Scientific, Dr Elaine Wong-Ho, discussed the importance of comprehensive genomic profiling (CGP) in precision oncology research and how the Oncomine™ Comprehensive Assay Plus,* initially available on the Ion GeneStudio™ S5 System, can now deliver next-day CGP results on the Ion Torrent™ Genexus™ System.
Dr Nicola Normanno then emphasized the growing importance of next-generation sequencing (NGS) in precision oncology, noting the increasing approval of biomarker-specific therapies. He presented studies supporting the value of CGP in increased biomarker detection for clinical trial enrollment, treatment decisions, and assessment of familial risk.
Finally, he presented performance studies of the Oncomine Comprehensive Assay Plus on both the GeneStudio S5 and Genexus systems for homologous recombination deficiency (HRD) assessment in ovarian cancer research samples. Preliminary data using the assay to detect relevant mutations across various tumor types was also shared.
*For research use only. Not for use in diagnostic procedures.
Learning objectives
Learn how Oncomine Comprehensive Assay Plus on the Genexus System makes next-day CGP accessible with an amplicon-based NGS approach.
Understand the relevance of CGP to detect a broad range of genomic alterations and genomic signatures, including HRD.
Hear how the assay performed in preliminary studies with ovarian cancer research samples.
Next-day CGP: Oncomine Comprehensive Assay Plus on the Genexus System
Meet the presenter
Dr Elaine Wong-Ho is Senior Manager, Product Management, Thermo Fisher Scientific, USA
Comprehensive genomic profiling and its importance
Dr Wong-Ho presented the need for CGP due to advances in precision medicine, highlighting the rapidly expanding list of relevant and emerging biomarkers across different cancer types.
Current guidelines recommend multi-gene NGS assays to evaluate multiple biomarkers simultaneously. The ability of CGP to meet this need is clear, stressed Dr Wong-Ho: “CGP enables the simultaneous analysis of a broad range of biomarkers into a single assay.”
And this need will only grow with time, she added: “As we gain a deeper understanding of the molecular mechanisms of tumor biology, CGP will be critical to help drive insights into advancing the future of personalized medicine.”
Summarizing the many advantages of bringing CGP in-house, she said, “As well as offering more control over tissue logistics and pre-analytical parameters, most importantly, it reduces turnaround times from weeks to days, which is crucial for timely and informative results” (Figure 1).
CGP research with the Oncomine Comprehensive Assay Plus
Dr Wong-Ho introduced the Oncomine Comprehensive Assay Plus which was first made available on the GeneStudio S5 system but is now available on the Genexus System. “The assay uses an amplicon-based approach to detect genomic alterations from 517 genes,” she explained, “including single nucleotide variants (SNVs), insertions and deletions (indels), copy number variants (CNVs), and fusions. It also detects genomic signature-based biomarkers such as HRD, tumor mutational burden (TMB), and microsatellite instability (MSI), facilitating simultaneous analysis of a broad range of biomarkers in one test to maximize insights in a timely manner.”
Dr Wong-Ho summarized the benefits of an amplicon-based CGP approach, pointing to a multi-center European study that demonstrated a high overall sequencing success rate of 94%, despite some samples only having 10% tumor cell content (1). Moreover, the Oncomine Comprehensive Assay Plus run on the GeneStudio S5 System demonstrated high analytical performance as a sensitive and specific assay for CGP with a greater than 95% concordance compared to orthogonal methods (1).
Oncomine Comprehensive Assay Plus’s approach to HRD assessment
The Oncomine Comprehensive Assay Plus measures both the causes and consequences of HRD in ovarian cancer research samples (Figure 2). On the causative side, Oncomine Comprehensive Assay Plus detects pathogenic variants in BRCA1 and BRCA2, long-established drivers of HRD.
On the consequences side, the assay incorporates the Genomic Instability Metric (GIM) – a novel metric that summarizes genomic scarring by analyzing patterns of unbalanced copy-number changes across autosomes. The result is a numerical score from 0 to 100. For ovarian cancer samples run on the GeneStudio S5 System, a GIM score above 16 is considered positive for genomic instability.
For HRD assessment, having either a known cause or consequence is sufficient for a sample to be considered HRD-positive. Only when there are no pathogenic BRCA1/2 variants and a low GIM score is a sample considered HRD-negative.
Dr Wong-Ho reported multiple customer-led studies demonstrating good analytical performance of the assay for HRD status, with studies by led by Dr Eloisa Jantus-Lewintre, Dr Annette Staebler and Dr Nicola Normanno showing consistent results (1-3) (Figure 3).
She also introduced an ongoing collaborative study presented at ASCO 2025 examining the agreement of Oncomine Comprehensive Assay Plus with the reference method (4). It will focus on BRCA1/2 mutational status, genomic instability, and overall HRD status.
Next-day CGP on the Genexus System
Now that the Oncomine Comprehensive Assay Plus is available on the Genexus System, she emphasized, “Next-day CGP is here with speed and simplicity.”
The Genexus System is a two-instrument NGS platform that automates the main steps of the NGS workflow with just two touchpoints and 20 minutes total of hands-on time (Figure 4). One touchpoint is for setting up the automated sample purification run on the Genexus Purification System and the other is for setting up the automated library preparation, sequencing, analysis and reporting on the Genexus Integrated Sequencer.
Figure 4. End-to-end workflow facilitates NGS democratization regardless of expertise
Performance of Oncomine Comprehensive Assay Plus on the Genexus System
Dr Wong-Ho presented R&D data showing that the Oncomine Comprehensive Assay Plus run on the Genexus System detects a broad range of genomic alterations with high sensitivity and specificity (Table 1).
Based on formalin-fixed paraffin-embedded (FFPE) samples (n=144) compared to orthogonal methods, AcroMetrix™ Oncology Hotspot Control, and Seraseq® Tri-Level Tumor Mutation DNA Mix v2.
“Oncomine Comprehensive Assay Plus also evaluates genomic signature-based complex biomarkers such as TMB and MSI,” she continued, “demonstrating high accuracy and sensitivity across different cancer types.” In particular:
Oncomine Comprehensive Assay Plus evaluates TMB with more than one megabase (Mb) of exonic coverage, showing high concordance to orthogonal assays.
The assay determines MSI status by assessing 76 microsatellite markers. Scores greater than or equal to 16 are considered MSI high and scores less than 15 are considered microsatellite stable (MSS).
GIM is used to accurately determine genomic instability with high overall percentage agreement between the Genexus and GeneStudio S5 systems.
Summary of Oncomine Comprehensive Assay Plus performance
Oncomine Comprehensive Assay Plus demonstrated excellent performance in detecting relevant variants across tumor types including SNVs, indels, fusions, and a range of CNV types from copy number loss (PTEN, MTAP) to arm level chromosomal changes (1p/19q). Additionally, genomic signatures like TMB, MSI, and GIM showed high concordance to orthogonal methods.
“The assay's high analytical performance makes it suitable for CGP of solid tumors, with the ability to detect relevant variants with high sensitivity and specificity,” said Dr Wong-Ho.
Dr Wong-Ho summarized the Oncomine Comprehensive Assay Plus as, “a valuable tool for CGP in precision oncology research.” Pointing to its highly automated workflow, next-day CGP results, and high-sequencing success rate, she concluded that the assay is, “a complete, end-to-end solution that simplifies bringing CGP in-house to make NGS more accessible to more laboratories.”
Access to CGP, and its Impact on Precision Oncology
Meet the presenter
Dr Nicola Normanno is Scientific Director, IRCCS Romagnolo Institute for the Study of Tumors, Italy
Impact of precision oncology drugs and biomarkers
Dr Normanno opened his presentation by noting the increasing approval of precision oncology drugs by regulatory bodies such as the FDA and EMA, highlighting the growing number of biomarker-specific therapies (Figure 5).
Despite differences in approval rates between the FDA and EMA, he noted that the rise in precision oncology drugs is expected to continue by cancer type, driving the need to identify specific biomarkers.
He also drew attention to the trend in tumor-agnostic drug approvals, targeting genomic alterations and genomic signatures like TMB and MSI across different tumor types – pointing to an increased need for large-panel genomic testing.
Updates in NGS recommendations
Dr Normanno reported updates to ESMO’s recommendations for testing in patients with advanced cancer:
In 2020, the ESMO Precision Medicine Working Group recommended the use of NGS in routine testing – but only in select tumor types such as non-small cell lung cancer (NSCLC), prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer.
Guidance stated that NGS testing should be performed in clinical research centers to increase the chances of clinical trial enrollment for patients.
The recommendations were updated in 2024 to include advanced breast cancer and some rare tumors such as gastrointestinal stromal tumors (GISTs), sarcoma, thyroid cancer and cancer of unknown primary (CUP) (6).
ESMO also recommended performing NGS to detect tumor-agnostic alterations in metastatic cancers where access to matched therapies is available (6).
Considerations for NGS panel size
On NGS panel size, he noted that, “the use of medium-sized panels (50 to 100 genes) is becoming more common due to their coverage, ease of use and cost-effectiveness. Large panels (>300 genes), on the other hand, allow for CGP with genomic signatures but have historically been more complex and costly” (Figure 6).
Turnaround times for small-panel NGS range from 4 to 40 days, with a median of 15 days, according to a European study (7). With large panels, he noted, we might expect even longer turnaround times, making adoption difficult in clinical practice.
CGP identifies more patients eligible for clinical trials
The RATIONAL study in Italy compared standard NGS testing, using small to medium panels, with CGP testing (8). Dr Normanno summarized the findings:
No significant difference was found in the identification of actionable biomarkers at ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) level I for standard NGS versus CGP testing.
CGP was better than standard NGS at identifying more ESCAT level II and III genomic alterations to match more patients for clinical trials.
Overall, less than 12% of patients, for which follow-up data were available, received a targeted therapy, based on the results of molecular analysis.
Reasons for non-receipt of therapy included deterioration or death before the molecular analysis was available, emphasizing the importance of timely NGS results, and lack of clinical trials or other pathways of access to drugs.
The need for both prognostic and predictive biomarkers
Dr Normanno discussed the importance of combining prognostic and predictive biomarkers for better stratification of patients as evident in the MARIPOSA trial (9).
EGFR mutated NSCLC patients with TP53 co-mutations – a poor prognostic marker – benefited from more aggressive, combined treatment versus single agent treatment (Figure 7).
However, the combined treatment benefit was less evident in EGFR mutated NSCLC patients with wild type TP53, suggesting that these patients could benefit from less intensive treatment, reducing unnecessary side effects.
In addition to understanding co-mutations for better stratification of patients, he also emphasized the importance of CGP for identifying genes involved in cancer susceptibility and inherited cancer syndromes to potentially reduce the burden of cancer in high-risk families.
HRD testing in ovarian cancer
In cases of advanced ovarian cancer, Dr Normanno emphasized the importance of identifying BRCA mutations and other HRD markers for predicting response to PARP inhibitors.
“It has been demonstrated that a fraction of ovarian cancer cases that do not carry BRCA mutations still have an HRD phenotype,” he added (10). “We need to identify these cases, because clinical trials have demonstrated these patients also benefit from PARP inhibitors” (Figure 8).
HRD Performance of Oncomine Comprehensive Assay Plus in a CGP research study
Performance studies for HRD testing with the Oncomine Comprehensive Assay Plus have been carried out on both the GeneStudio S5 and Genexus systems for advanced ovarian cancer research samples.
On the GeneStudio S5 System, a retrospective multicenter study ran n=100 stage III-IV ovarian cancer research samples:
Oncomine Comprehensive Assay Plus showed good overall concordance with the reference method for:
BRCA1/BRCA2 mutational status
Genomic instability using GIM
HRD status (90.7% overall concordance)
HRD status with the assay demonstrated similar trends in progression-free survival relative to the reference method in this clinical research study.
On the Genexus System, preliminary data from n=24 stage III-IV ovarian cancer research samples were generated:
Oncomine Comprehensive Assay Plus had good overall concordance with the reference method and the assay on the GeneStudio S5 System for:
BRCA1/2 mutational status
Genomic instability status using GIM
HRD status (90.9% overall concordance with both methods)
Since the Oncomine Comprehensive Assay Plus is a CGP assay, biomarker performance on the Genexus System was also tested on 15 pre-characterized non-ovarian cancer samples.
Preliminary studies showed 100% concordance with orthogonal methods for SNVs, indels, CNVs, and fusions.
Conclusions
Dr Normanno stressed the importance of access to biomarker testing and approved precision medicines for all cancer patients in the future.
He reiterated that the Oncomine Comprehensive Assay Plus on the Genexus System showed good concordance with reference methods for ovarian cancer testing and has encouraging preliminary data in pan-cancer research samples.
Dr Normanno ended by highlighting the significance of rapid turnaround times for CGP assays. “The great advantage of the Oncomine Comprehensive Assay Plus on the Genexus System is really the possibility to get rapid results from CGP,” he said.
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References
- E Jantus-Lewintre et al., “Multicenter in-house evaluation of an amplicon-based next-generation sequencing panel for comprehensive molecular profiling,” Mol Diagn Ther 29, 2 (2025).
- A Staebler, “Genomic instability metric (GIM) from Oncomine Comprehensive Assay Plus,” Oncomine World Webinar (2023).
- N Normanno, “Future clinical perspective of HRD testing in ovarian cancer samples using NGS CGP,” Genome Web Webinar (2023).
- M Gupta et al., “Assessment of Homologous Recombination Deficiency and BRCA Status in Ovarian Cancer: Analytical Performance and Relevance of a Decentralized NGS Assay for Comprehensive Genomic Profiling”, poster #3130 presented at ASCO Annual Meeting (2025).
- J Mateo et al., “Delivering precision oncology to patients with cancer,” Nat Med, 28, 4 (2022).
- M Mosele et al., “Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group,” Ann Oncol, 37, 7 (2024). PMID: 38834388
- N Normanno et al., “Access and quality of biomarker testing for precision oncology in Europe,” Eur J Cancer, 176 (2022). PMID: 36194905
- N Normanno et al., “Current practice of genomic profiling of patients with advanced solid tumours in Italy: the Italian Register of Actionable Mutations (RATIONAL) study,” Eur J Cancer, 187 (2023). PMID: 37167765
- B Cho et al., “Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results from MARIPOSA, a phase III, global, randomized, controlled trial,” LBA14 presented at ESMO Annual Meeting (2023).
- P Konstantinopoulos et al., “Homologous recombination deficiency: Exploiting the fundamental vulnerability of ovarian cancer,” Cancer Discov 5, 11 (2015). PMID: 26463832
