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Comprehensive genomic profiling for solid tumors brings precision medicine to the bedside


read time: 4 minutes

In the past 2 decades, treatment of solid tumors has undergone nothing short of a revolution, driven by developments in genomics. Genomic analysis has made it clear that cancer is a genetic disease and that mutations, not location, is the best way to characterize and develop treatment for tumors. Genomic testing has made it possible to rapidly and definitively identify those mutations, allowing for mutation-specific treatment with the shortest possible delay.

But with the explosion in understanding of cancer genomics, there has come the need for more comprehensive and efficient forms of genomic testing. Physicians may be hard-pressed to know where to start in the hunt for the causative mutation, and testing for a series of single mutations may lead to delays in treatment if the first (or second, or third) test comes up negative.

Comprehensive genomic profiling (CGP) addresses these challenges by testing for hundreds of mutations at once. Assessing both rare and prevalent biomarkers with just one biopsy sample increases the chances of finding cellular changes that are treatable for thyroid, colorectal, bladder, melanoma, breast, gastrointestinal, ovarian, and prostate solid tumor cancers.

Advances in understanding

The clinical application of genetics to cancer treatment took off in 1998, with the development of a monoclonal antibody (trastuzumab) that inactivates human epidermal growth factor receptor 2 (HER2). Overexpression of HER-2 is a key feature of some forms of metastatic breast cancer, and the antibody specifically targets overexpressing cells. Because of that specificity, a positive diagnostic test for HER2 is critical for its use.

The approval of trastuzumab, along with the diagnostic test, served as a model for the extraordinary growth in targeted cancer therapies and diagnostics in use today. Scores of both common and rarer mutations have been identified, and dozens of mutation-specific treatments approved, with new mutations being identified and new treatments developed every year.

Mutations are not tumor-specific: for instance, mutations in the BRAF gene are associated with melanoma, thyroid, and colorectal tumors. MSH2 mutations are found in both breast and gastrointestinal tumors. That means, for instance, that a drug developed to target the BRAF mutation in melanoma may also find utility in thyroid tumors, but it also greatly widens the range of potential mutations that may be involved and should be tested for in any  type of tumor.

Advances in testing

Comprehensive genomic profiling is a solution to the challenge of the growing number of mutations potentially implicated in any one tumor type. In just  one test, an expanded CGP panel detects information across hundreds of genes.

The potential for CGP to improve care has been shown in multiple studies, including one of 521 patients with solid tumors who were tested with a hotspot assay and a CGP assay. The comparison showed that 214 (41%) had at least one actionable gene alteration that had not been identified in the hotspot assay. Of those 214 patients, 19% underwent matched therapy and had significantly improved overall survival compared with those treated with unmatched therapy.1

In addition to a large and growing number of discrete mutations, CGP panels can also provide insight into 2 critical biomarkers with therapeutic predictive value.

  • Tumor mutational burden (TMB) is the number of mutations per megabase of DNA. Tumors with a higher TMB have been shown to be more responsive to treatment with certain immunotherapies.2
  • A microsatellite is a short stretch of repetitious DNA, scattered throughout the genome. Microsatellite instability (MSI) refers to a change in the number of repeats within a microsatellite after a cell is formed. A high rate of MSI within a tumor is a biomarker for susceptibility to checkpoint inhibitors.

Tumor testing with CGP helps the physician navigate emerging therapies beyond the current standard of care. With CGP, the physician receives the most up-to-date information about their patient’s solid tumor(s). The right laboratory will also provide information about matching treatments—both those approved and those in clinical trials—that enable precision treatment to begin as soon as possible. In this way, comprehensive genomic profiling can bring the treating physician to the cutting edge of modern cancer treatment, and help to offer the patient the most effective treatment for their solid tumor.


1. Kopetz S, Mills Shaw KR, Lee JJ, 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 Precis Oncol. doi:10.1200/PO.18.00213

2. Cristescu R, Aurora-Garg D, Albright A, et al. Tumor mutational burden predicts the efficacy of  pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022;10(1):e003091. doi:10.1136/jitc-2021-003091

Page Published: March 06, 2024