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A Comprehensive Answer for Cancer: Is Comprehensive Genomic Profiling Always the Right Approach?

What is comprehensive genomic profiling (CGP)?

CGP is the simultaneous detection of all classes of genomic alterations across hundreds of genes with a single test – and a single sample. This forward-thinking technique was enabled by the advent of next-generation sequencing (NGS) and its ability to deliver ultra-high throughput and scalability.


Why is CGP so important for precision oncology research?

Cancer is “a disease of the genome,” driven by the sequential accumulation of genetic and epigenetic changes in oncogenes and tumor suppressor genes. The more we learn about cancer, the more such changes we discover – and the more these variants, or biomarkers, become relevant to translational and clinical research into new cancer treatments. It’s now clear that many of them must be interrogated together so that we can understand as much about the molecular makeup of a tumor as possible. This type of simultaneous interrogation is sometimes only possible using CGP.

Take, for example, breast cancer, in which we have long been testing single-gene biomarkers, such as ERBB2 (Her2) amplification, BRCA1 and BRCA2 mutations, and, more recently, PIK3CA mutations. Now, we are also beginning to examine homologous recombination repair (HRR) pathway gene mutations and complex biomarkers such as genomic instability to assess HRR deficiency (HRD).


Is CGP a technique for every lab?

Not every approach to CGP is suitable for every laboratory. Until recently, labs’ ability to generate the increasing amounts of CGP data needed has been hindered by the technical limitations of the available techniques. Some hybrid capture-based NGS CGP techniques are complex workflows with up to five different instruments (and five corresponding sets of software) that must be stitched together. This requires significant expertise and extensive hands-on lab work – thus preventing broader adoption of the technique.

But now, Thermo Fisher’s new and enhanced Ion Torrent Oncomine Comprehensive Assay Plus comes as a complete, highly automated (60 minutes of hands-on time) solution with streamlined data analysis and reporting – all from a single supplier, enabling endto-end protocols. This will allow many more labs to implement CGP.


Is CGP the right choice for all cancer sample profiling?

Not necessarily; based on pure common sense, one size does not fit all. Let’s take non-small cell lung cancer (NSCLC) as an example. All biomarkers relevant for clinical research into NSCLC can be tested by one 50-gene targeted panel. It’s cheaper, faster, and requires less sample input than CGP – which is critical in NSCLC, where “tissue is still an issue.”

Some hybrid capture-based NGS CGP techniques require so much tissue that over half of normal clinical research samples cannot be analyzed (1). If all of the necessary information can be obtained from a single targeted panel, why risk attempting CGP and potentially ending up with no results at all? Even in genomic profiling, bigger is not always better.


When is CGP the right choice?

There are four key scenarios in which comprehensive genomic profiling is most impactful.

1. You have evaluated your sample with a smaller targeted panel and the results came back negative. Reflexing to CGP increases the chance of finding less common variants with potential relevance.

2. You need to analyze complex multi-gene biomarkers as well as single-gene biomarkers. In many scenarios, complex multi-gene biomarkers such as microsatellite instability (MSI) or tumor mutational burden (TMB) are required as well as mutations, fusions, and copy number variants. Clinical immuno-oncology research (for example, using colon cancer samples) is one such scenario.

3. You are assessing the HRR pathway. HRD can be assessed using two main strategies: i) detection of genetic causes, such as germline or somatic mutations of HRR genes, including BRCA1 and BRCA2; and ii) evaluation of “genomic scarring” representing genomic instability, such as the analysis of genome-wide loss of heterozygosity

4. You are working with cancers of unknown primary. Interrogation with a broad, comprehensive test will deliver maximum insights in the shortest amount of time, potentially uncovering information that can help identify the cancer.


Which is the right CGP solution for you?

Although there are multiple CGP solutions on the market today, many are technically complex and require large amounts of starting sample material. They also are not truly “comprehensive” in that they may not enable analysis of all complex biomarkers or mutational signatures – despite the fact that they are becoming standard in some clinical research.

That’s why Thermo Fisher Scientific developed the Ion Torrent Oncomine Comprehensive Assay Plus. Requiring only 20 ng of formalin-fixed, paraffin embedded sample – the lowest sample requirement for CGP on the market – it analyzes over 500 genes. Including both DNA- and RNA-based variants and all relevant single- and multi-gene biomarkers, the Oncomine Comprehensive Assay Plus is truly comprehensive genomic profiling, without compromises.

Learn more in our on-demand webinar: Comprehensive Genomic Profiling using the Oncomine Comprehensive Assay Plus System

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Thermo Fisher Scientific Staff
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Thermo Fisher Scientific Staff