EGFR Mutation Testing

EGFR (the gene that produces a protein called epidermal growth factor receptor) is abnormal or mutated, in about 10%[1]Lovly, C., L. Horn, W. Pao. 2015. EGFR in Non-Small Cell Lung Cancer (NSCLC). My Cancer Genome (Updated June 2015). of patients with non-small cell lung cancer (NSCLC) and in nearly 50%[2]Lovly, C., L. Horn, W. Pao. 2015. EGFR in Non-Small Cell Lung Cancer (NSCLC). My Cancer Genome (Updated June 2015). of lung cancers arising in those who have never smoked.

In NSCLC matching a specific targeted drug to the identified driver mutation for an individual patient has resulted in significantly improved therapeutic efficacy, often in conjunction with decreased toxicity. In advanced NSCLC, the presence of an EGFR driver mutation or acquired resistance mutation T790M confers sensitivity to EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib, and osimertinib. The use of EGFR TKIs is based upon the detection of these mutations.

The EGFR Mutation and Cancer

These mutations occur within EGFR exons 18-21, which encodes a portion of the EGFR kinase domain. EGFR mutations are usually heterozygous, with the mutant allele also showing gene amplification. Approximately 90% [3]Lovly, C., L. Horn, W. Pao. 2015. EGFR in Non-Small Cell Lung Cancer (NSCLC). My Cancer Genome (Updated June 2015). of these mutations are exon 19 deletions or exon 21 L858R point mutations. These mutations increase the kinase activity of EGFR, leading to hyperactivation of downstream pro-survival signaling pathways.

Regardless of ethnicity, EGFR mutations are more often found in tumors from female never smokers with adenocarcinoma histology. However, EGFR mutations can also be found in other subsets of NSCLC, including former and current smokers as well as in other histologies. In the vast majority of cases, EGFR mutations are non-overlapping with other oncogenic mutations found in NSCLC, such as KRAS mutations or ALK rearrangements.

Schematic of EGFR mutations. EGFR Mutation Testing.

Schematic of EGFR mutations. Exons 18–21 of the EGFR kinase domain are depicted. Mutations above the schematic are associated with sensitivity to EGFR TKIs. Mutations listed below the schematic are associated with EGFR TKI resistance.

Note: a While most exon 20 insertions are associated with decreased EGFR TKI sensitivity, the EGFR A763_Y764insFQEA mutation is an exception and has been associated in retrospective studies with increased EGFR TKI sensitivity (Yasuda et al. 2013).

Traditional Testing for EGFR

Activating mutations in the gene encoding epidermal growth factor receptor (EGFR) can confer sensitivity to EGFR tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer (NSCLC). Testing for mutations in EGFR is therefore an important step in the treatment-decision pathway.

Traditionally, tissue biopsy has been the standard method used for EGFR mutation testing. Many of the methods specifically detect the most common EGFR mutations. The development of targeted mutation testing methods and commercially available test kits has enabled sensitive, rapid and robust analysis of clinical samples. The use of diagnostic methods, subsequent to sample micro dissection, has also ensured that identification of more rare, uncommon mutations is now feasible. Cytology samples including fine needle aspirate and pleural effusion can be used successfully to determine EGFR mutation status provided that sensitive testing methods are used. The presence of EGFR mutations predicts the sensitivity to EGFR tyrosine kinase inhibitors in a molecularly defined subset of non-small cell lung cancer (NSCLC) patients. For this reason, EGFR testing of NSCLC is required to provide personalized treatment options and better outcomes for these patients. Targeted therapy blocks the growth of cancer cells by interfering with specific pathways needed for carcinogenesis rather than by broadly interfering with rapidly dividing cells (eg, with traditional chemotherapy).

As surgery specimens are not available in the majority of NSCLC, other currently available DNA sources are small biopsies and cytological samples; however, they often provide limited and low-quality DNA material and inconclusive results.

Up to 25% [4]JCO 2015 33 (25) Future Oncol 2015 11(3) of tissue biopsies do not have enough cancer cells to analyze, leading to inconclusive results. Tissue biopsies can be painful, carry risks such as bleeding or infection, and increase the emotional and physical burden of cancer care. Additionally, tissue biopsy results may take up to 30 days to receive, potentially delaying the information needed to select the appropriate treatment. Scans and tissue biopsies add significant cost over the course of treatment and may add to cancer-related stress and anxiety.

Liquid Biopsy Tests for EGFR Mutations

Certain fragments of DNA shed by tumors into the bloodstream can potentially be used to noninvasively detect EGFR driver and resistance mutations, monitor responses to treatment and disease progression.

In order to address issues associated with tissue biopsy, the use of surrogate sources of DNA, such as blood or urine samples, which contain circulating tumor DNA (ctDNA), has emerged as a new strategy for tumor genotyping.

For most tumors, a tissue biopsy is challenging – it is costly, painful, or potentially risky for the patient.

Today, circulating tumor DNA (ctDNA) may hold benefits that the traditional cancer diagnostic methods or tissue biopsies can’t offer such as detection through urine or blood without an invasive procedure like surgery. The evolution of sensitive ctDNA detection technologies has enabled the development of liquid biopsies with many clinical applications.

Circulating tumor DNA (ctDNA) liquid biopsy allows us to understand specifically what kind of molecular changes are happening in the tumor in real time.

Trovagene Precision Cancer Monitoring


The use of Trovagene’s urine or blood liquid biopsy is only intended for detection and monitoring of mutations in patients previously diagnosed with cancer. It is not intended for screening of asymptomatic patients to diagnose cancer.

The Trovera Difference

Trovera liquid biopsy tests provide actionable information about mutations associated with common solid tumor cancers to aid physicians in choosing the right treatment for the right patient at the right time.



Noninvasive identification of clinically actionable mutations to inform treatment decisions.



Highly sensitive analysis of tumor dynamics.



Response to therapy, emergence of resistance mutation(s), disease progression and minimal residual disease.

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References   [ + ]

1, 2, 3. Lovly, C., L. Horn, W. Pao. 2015. EGFR in Non-Small Cell Lung Cancer (NSCLC). My Cancer Genome (Updated June 2015).
4. JCO 2015 33 (25) Future Oncol 2015 11(3)