What Is Comprehensive Genomic Profiling?
Comprehensive genomic profiling (CGP) is a next-generation sequencing (NGS) approach that uses a single assay to assess hundreds of genes including relevant cancer biomarkers, as established in guidelines and clinical trials, for therapy guidance.
Detect Multiple Biomarkers in a Single Assay
CGP can detect biomarkers at nucleotide-level resolution and typically comprises all major genomic variant classes (single nucleotide variants, indels, copy number variants, fusions, and splice variants). Additionally, CGP can detect genomic signatures such as TMB and MSI (tumor mutational burden and microsatellite instability, respectively), maximizing the ability to find clinically actionable alterations.
Consolidate Testing to Save Time and Precious Samples
CGP consolidates biomarker detection into a single multiplex assay, eliminating the need for sequential testing. With a single test, you can assess the most prevalent as well as rare biomarkers. By assessing all biomarkers at once, you may increase chances of finding an actionable alteration. This potentially provides faster results, limits the input of precious biopsy samples, and may reduce the risks and cost associated with rebiopsy.1,2
Identify Actionable Alterations
CGP can offer both actionable and potentially actionable results to help identify more effective therapeutic paths and innovative clinical trial options for cancer patients. When tissue biopsies are unavailable, CGP from liquid biopsy may provide helpful information about a tumor's genomic make-up. CGP using tissue and liquid biopsy together may reveal more insights into a tumor's composition.3,4
Percentage of Potentially Actionable Alterations
Multiple studies have demonstrated the ability of CGP to identify potentially clinically relevant genomic alterations, across different tumor types.
| Potentially Actionable Variants Identified in Patient Samples | Patient Cohort | Author |
|---|---|---|
 |
Single center, prospective study with 339 patients. Refractory cancers, multiple types: ovarian (18%), breast (16%), sarcoma (13%), renal (7%) and others | Wheeler et al 20166 |
 |
Prospective study with 100 patients, diverse-histology, rare, or poor-prognosis cancers | Hirschfield et al 20167 |
 |
Prospective study with 10,000 patients with advanced cancer aross a vast array of solid tumor types | Zehir et al 20178 |
 |
Retrospective study with 96 patients across multiple tumor types | Reitsma et al 20199 |
 |
6,832 NSCLC patients | Suh et al 201610 |
The % of actionable alterations identified in each study varies according to patient cohort, study type, CGP panel used, and criteria for categorizing a genomic alteration as actionable.
Data on file.
Improving Patient Outcomes with CGP
* Ongoing clinical trials globally linked to a cancer biomarker11
* Comprehensive list includes therapies not associated with a genomic biomarker (eg, protein biomarkers)
What Do the Experts Say About Comprehensive Genomic Profiling?
Listen to Marjolijn Ligtenberg, Pathologist, Laboratory of Tumor Genetics, Radboud University Medical Center, and others discuss the value CGP offers to patients and healthcare providers.
How CGP Compares to Other Sequencing Methods
CGP vs Single-Gene Assays
Single-gene assays are limited to a single biomarker. Many times these assays do not cover the entire gene sequence, with the risk of missing important gene alterations.13
An iterative single-gene testing approach can lead to tissue depletion and repeat biopsies.13,15,16
CGP vs Targeted Panels
Targeted panels typically offer coverage of specific genes instead of the entire coding sequence. As a result they can miss important alterations.7
A comprehensive single assay that assesses a wide range of biomarkers increases the chances of obtaining relevant information vs. targeted panels.
CGP vs Exome Sequencing
Not only can whole-exome sequencing be cost-prohibitive when developing personalized therapies, but it can also lead to inadequate coverage to detect important variants in lower frequencies due to the need for high amounts of sequencing.17-21
There are a lot of very impressive novel therapies coming on the market with new fusions that we need to detect.
At OmniSeq, we've adopted comprehensive genomic profiling as our test of choice so we could look at multiple biomarkers on a minimum of specimens to get a single consolidated report.
A solid CGP assay is, in my opinion, inclusive of both DNA and RNA analysis. There is mounting data that clinically relevant variants can be missed by DNA analysis alone.
The change from single-gene or single-biomarker testing to a comprehensive panel based approach has been driven by...factors that include inherent efficiency of a single comprehensive panel, which is key among cancers and other samples that have limited tissue.
It is important for CGP to include DNA and RNA targets. RNA fusions are very important in some cancers and you need to see the exact RNA fusion.
Precision Medicine Through Comprehensive Genomic Profiling
NGS can power insights by examining hundreds of cancer genes in a single assay. Using CGP with liquid biopsies provides a quicker, less invasive, and less risky sample source for understanding complex cancers. Watch the video and learn how a complete suite of CGP offerings used within your lab can deliver faster precision medicine.
Reasons to Bring CGP In-House
Adding comprehensive genomic profiling to your lab’s in-house test menu can provide a number of added benefits. These include:
Delivering results faster (as compared to send-out services)
Reducing Quantity Not Sufficient (QNS) rates
Increasing number of informed cases
Building a database for future studies
Amplifying the role of the pathologists on the care team
CGP Solution
TruSight Oncology Comprehensive (EU) is the first CE-marked IVD test kit for comprehensive genomic profiling based on DNA and RNA that consolidates multiple iterative tests into one.
Learn MoreConsult with an expert to learn more about CGP
Hear from Cancer Experts
Carlo B. Bifulco, MD: Comprehensive Genomic Profiling
Carlo B. Bifulco, MD provides his point of view on CGP as an approach for assessing biomarkers for therapy selection and clinical trial enrollment.
Professor Andrew Beggs Discusses CGP
Professor Andrew Beggs of the University of Birmingham shares his point of view on comprehensive genomic profiling as an approach for assessing biomarkers for therapy selection and clinical trial enrollment.
Sandip Patel, MD: Comprehensive Genomic Profiling
Sandip Patel, MD, from UCSD Moores Cancer Center discusses why he believes CGP is poised to become standard of care in oncology.
Dr. David Eberhard: Utility of CGP
This educational video explains how CGP provides cancer patients and oncologists with a powerful testing approach to help identify biomarkers for therapy selection and eligibility for clinical trials.
Flexible Capabilities to Enable Comprehensive Genomic Profiling
AMP 2020 panel speakers describe implementation of a CGP assay at their institutions and discuss the keys to offering CGP testing so that data access and turn-around time can benefit patients.
Comprehensive Genomic Profiling: A New Paradigm in Oncology
A webcast series from the ESMO Virtual Congress 2020 Industry Satellite Symposium.
Clinical Implications of Plasma-Based Genotyping With the Delivery of Personalized Therapy in Metastatic Non-Small Cell Lung Cancer
Genomic and Transcriptomic Profiling Expands Precision Cancer Medicine: the WINTHER Trial
Feasibility and Utility of a Panel Testing for 114 Cancer-associated Genes: A Hospital-based Study
References
- Pennel AP, Mutebi A, Zheng-Yi Z, et al. Economic Impact of Next-Generation Sequencing Versus Single-Gene Testing to Detect Genomic Alterations in Metastatic Non–Small-Cell Lung Cancer Using a Decision Analytic Model. JCO Precis Oncol. 2019. doi.org/10.1200/PO.18.00356.
- Lindeman NI, Cagle PT, Aisner DL, et al. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Mol Diagn. 2018 Mar;20(2):129-159.
- Aggarwal C, Thompson JC, Black TA, et al.. Clinical Implications of Plasma-Based Genotyping With the Delivery of Personalized Therapy in Metastatic Non-Small Cell Lung Cancer. JAMA Oncol. 2019 Feb 1;5(2):173-180.
- Tukachinsky H, Madison RW, Chung JH, et al. Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms. Clin Cancer Res. 2021 Feb 8:clincanres.CCR-20-4805-E.2020.
- Wheler JJ, Janku F, Naing A et al Cancer Therapy Directed by Comprehensive Genomic Profiling: A Single Center Study. Cancer Res. 2016 Jul 1;76(13):3690-701.
- Hirshfield KM, Tolkunov D, Zhong H. Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers. Oncologist . 2016 Nov;21(11):1315-1325.
- Zehir A, Benayed R, Shah R et al Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med . 2017 Jun;23(6):703-713.
- Reitsma et al., 2019. Effect of a Collaboration Between a Health Plan, Oncology Practice, and Comprehensive Genomic Profiling Company from the Payer Perspective. Journal of Managed Care & Specialty Pharmacy. 2019 Jan 11:1-10
- Suh JH, Johnson A, Albacker L, et al. Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials. Oncologist. 2016 Jun;21(6):684-91.
- NIH National Cancer Institute. Cancer Drugs - National Cancer Institute. cancer.gov website. https
: / / www . cancer . gov / about - cancer / treatment / types / targeted - therapies - fact-sheet. Accessed May 28, 2021. - NIH US National Library of Medicine. Home - ClinicalTrials.gov. Find a study. https://www.clinicaltrials.gov/. Search terms included “genetic”, “genomic”, “DNA”, or “RNA”. Accessed January 25, 2021.
- Kopetz S, Shaw K, Lee J, et al. Use of a Targeted Exome Next-Generation Sequencing Panel Offers Therapeutic Opportunity and Clinical Benefit in a Subset of Patients With Advanced Cancers. JCO Precision Oncology. 2019;3:1-14.
- Drilon A, Wang L, Arcila ME, et al. Broad, Hybrid Capture-Based Next-Generation Sequencing Identifies Actionable Genomic Alterations in Lung Adenocarcinomas Otherwise Negative for Such Alterations by Other Genomic Testing Approaches. Clin Cancer Res. 2015;21(16):3631-363.
- Ali SM, Hensing T, Schrock AB, et al. Comprehensive Genomic Profiling Identifies a Subset of Crizotinib-Responsive ALK-Rearranged Non-Small Cell Lung Cancer Not Detected by Fluorescence In Situ Hybridization. Oncologist. 2016 Jun;21(6):762-70.
- Lim C, Tsao MS, Le LW, et al. Biomarker testing and time to treatment decision in patients with advanced nonsmall-cell lung cancer. Annals of Oncology. 2015;26(7):1415-1421.
- Yu TM, Morrison C, Gold EJ, et al. Multiple Biomarker Testing Tissue Consumption and Completion Rates With Single-gene Tests and Investigational Use of Oncomine Dx Target Test for Advanced Non-Small-cell Lung Cancer: A Single-center Analysis. Clin Lung Cancer. 2018 Jan;20(1):20-29.e8.
- Buchhalter I, Rempel E, Endris V, et al. Size matters: Dissecting key parameters for panel-based tumor mutational burden analysis. Int J Cancer. 2019;144(4):848-858 .
- Chalmers ZR, Connelly CF, Fabrizio D, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017;9(1):34.
- Pestinger V, Smith M, Sillo T, et al. Use of an integrated pan-cancer oncology enrichment NGS assay to Measure tumour mutational burden to detect clinically actionable variants. Mol Diagn Ther. 2020 Jun;24(3):339-349.
- Heydt C, Rehker J, Pappesch R, et al. Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing. Sci Rep. 2020 Jul 9;10(1):11387.
- Vanderwalde A, Spetzler D, Xiao N, et al. Microsatellite instability status determined by next-generation sequencing and compared with PD-L1 and tumor mutational burden in 11,348 patients. Cancer Med. 2018 Mar;7(3):746-756. Med. 2018 Mar;7(3):746-756.