What is comprehensive genomic profiling?
Comprehensive genomic profiling, or CGP, is the simultaneous detection of all classes of genomic alterations across hundreds of genes with just one test. This ability to interrogate such huge quantities of genetic information at one time is a massive departure from the very first genetic test developed in the 1950s, called karyotyping, and consisted of staining, sorting and counting chromosomes to identify cases of Down’s Syndrome3. While the evolution of genetic testing has evolved very quickly over the last 55 years, the invention of next-generation sequencing in 2006 proceeded to revolutionize the biological sciences with its ability to deliver ultra-high throughput and scalability.
Why is comprehensive genomic profiling promising for oncology research?
Cancer is a disease driven by the sequential accumulation of genetic and epigenetic changes in oncogenes and tumor suppressor genes.2 The onset of these genomic alterations often metastasizes very quickly, creating a situation in which the time is of essence, and the ability to gain genomic insights is critical. Because comprehensive genomic profiling enables detection of variants across hundreds of genes at the same time, the comprehensive analysis will provide abundant data to work with.
The advent of next-generation sequencing along with the increasing adoption of large-scale tumor molecular profiling programs has revolutionized the field of precision oncology1. research, where the comprehensive nature of the insights, and quick turnaround time due to ability to eliminate iterative testing will provide researchers with an abundance of insights to work with.
Is comprehensive genomic profiling right for all cancer samples?
However, one must also remember the end goal. The purpose of profiling tumor samples is to better understand the specific drivers of mutagenesis in these samples. Cancer is a heterogeneous disease on many levels. Therefore, it follows that the drivers for one tumor sample or type, will likely differ from another. Due to this tumor heterogeneity, it begs the question, why would one choose to test these samples with the same test? A better approach would be to mindfully select the most appropriate test for the tumor, ensuring the genomic insights gained would be relevant and specific.
When is comprehensive genomic profiling the right solution?
There are four scenarios in which comprehensive genomic profiling would be most impactful. First, if you are working with cancers of unknown primary. Interrogation with a broad, comprehensive test would deliver maximum insights in the least amount of time, potentially uncovering information that would help identify the cancer. Second, if you are conducting oncology research for targeted therapies and immunotherapies, a comprehensive genomic profiling solution can deliver all these biomarker insights, including TMB and MSI, in one test. Third, if you have evaluated your sample with a smaller targeted panel and the results come back negative, reflexing to a large CGP test expands the genomic profiling with more alterations, increasing the odds of positive results. Last, assessment of the homologous recombination repair (HRR) genes and pathway is becoming a hot area of focus. Now you can detect single-gene and multiple gene biomarkers, including deficiencies in the HRR pathway, with just one assay.
Which is the right comprehensive genomic profiling solution for you?
There are multiple solutions on the market today for comprehensive genomic profiling. However, Thermo Fisher Scientific sought to improve on those solutions and developed the Ion Torrent Oncomine Comprehensive Assay Plus. Requiring only 20 ng FFPE sample, which is the lowest sample requirement for CGP, 517 DNA and RNA genes can be interrogated simultaneously for all classes of variants including loss-of-function variants such as gene-level loss-of-heterozygosity (LOH). Mutational signatures such as TMB and MSI can be detected, deficiencies in homologous recombination repair (HRR) and genomic instability through sample-level loss of heterozygosity (LOH) can be assessed, and an automated, streamlined sample-to-report workflow delivers insights and a mutational signature plot without additional analysis by third party software.
Malone, E.R., Oliva, M., Sabatini, P.J.B. et al.Molecular profiling for precision cancer therapies. Genome Med 12, 8 (2020). https://doi.org/10.1186/s13073-019-0703-1
Lahouel, K. PNAS January 14, 2020 117(2) 857-864 https://doi.org/10.1073/pnas.1914589117