What Is Exon 20?
Exons are minute parts of DNA (deoxyribonucleic acid) that contain instructions for making proteins. Exon 20 simply means the 20th exon in a gene sequence. These sections help the body produce proteins that are important for normal cell functions.
Exons are the coding parts of genes. They carry the information needed to build proteins that help cells grow, repair, and perform different tasks in the body.
Exon 20 also plays an important role in mRNA (messenger RNA) splicing. mRNA is created when DNA is transcribed. This mRNA then serves as a template for protein synthesis.
Before proteins are made, mRNA goes through splicing. During this step:
- Non-coding regions known as introns are removed.
- Coding regions known as exons are joined together.
Exon 20 helps ensure these coding sections are joined correctly, so the correct protein is produced.
What Is an EGFR Mutation?
A mutation is a change in the DNA sequence. These changes can affect how cells grow and function.
The epidermal growth factor receptor (EGFR) is a protein found on the surface of many cells, including skin cells. It helps control cell growth and multiplication.
The EGFR gene gives instructions for making the EGFR protein. Normally, this gene becomes active only when the body needs new cells.
However, in some conditions, such as non-small cell lung cancer (NSCLC), the EGFR gene mutation causes the EGFR protein to keep signaling cells to grow, even when they should stop. This leads to uncontrolled cell growth, which can form tumors.
The abnormal EGFR gene can also act as a biomarker (tumor marker). Doctors can detect this marker through laboratory tests to help diagnose and guide cancer treatment.
Cancer cells that contain this abnormal gene are called EGFR-positive. This tumor marker was first identified for the targeted management of EGFR-positive lung cancer. NSLC (non-squamous lung carcinoma) is the most common type of lung cancer with EGFR-positive genes. Small-cell lung cancer is the second most common cancer with this gene mutation.
What Is an EGFR Exon 20 Insertion Mutation?
The mutation occurring in the EGFR gene is referred to as an exon 20 insertion mutation. The EGFR gene has several exons; changes can occur in any of them. In this mutation, a small excess of genetic material is inserted into the exact location of exon 20 in the gene. The most common type of EGFR mutation involves a deletion of exons 19 and 21. Exon 19 and 21 mutations are common, accounting for approximately 85 percent of EGFR-mutated lung cancers.
The exon 20 insertion mutation is less common, occurring in approximately 4 % of lung cancer patients. Among individuals with EGFR mutations, about 4 to 12 percent have an exon 20 insertion mutation, making it the third most common type of EGFR mutation. The exon 20 insertion mutation is rare, even among individuals with EGFR mutations. Also, this mutation is associated with a poor prognosis. Even the targeted therapies used in managing EGFR mutations, such as tyrosine kinase inhibitors, are ineffective in individuals with an exon 20 insertion mutation.
Who Is at High Risk for EGFR-Positive Lung Cancer?
Generally, individuals are not born with an exon 20 insertion mutation. However, a small piece of genetic material is accidentally added to the EGFR gene during its lifetime. The exact cause of this is unknown.
Although few individuals are at high risk of developing EGFR-positive lung cancer:
- Individuals who have never smoked or smoked only a little.
- Individuals with lung adenocarcinoma (a type of NSCLC cancer).
- Young adult with NSCLC.
- Women.
- Individuals with Asian or East Asian heritage.
Why Is It Essential to Know the EGFR Mutation Type?
Knowing the type of EGFR gene mutation allows the appropriate treatment for non-small cell lung cancer (NSCLC) to be determined. For instance, a mutation in EGFR will make targeted therapies called tyrosine kinase inhibitors very effective. Cancer is caused by exon 20 mutations that do not respond to tyrosine kinase inhibitors. So, depending on the mutation type, the medication will vary to provide an effective treatment.
The medications generally used in cancer with an exon 20 mutation that provide successful results include:
- Erlotinib.
- Osimertinib.
- Afatinib.
- Gefitinib.
- Dacomitinib.
- Amivantamab.
What Is the Treatment for the Exon 20 Mutation?
In most cases, NSCLC is diagnosed in advance. In such cases, treatment will not completely cure the disease. So, the treatment will aim to ease the symptoms and control the spread of cancer. Traditionally, chemotherapy was the most effective treatment for individuals with NSCLC. With targeted therapies, researchers have discovered that some EGFR inhibitors work well for people with EGFR mutation cancer.
The treatment options include:
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Chemotherapy:
As EGFR inhibitors do not work for individuals with the exon 20 insertion mutation, chemotherapy was used as the first-line treatment for individuals with advanced stages of cancer. If the cancer is less advanced, radiation therapy or surgery may also be suggested. Immunotherapy may work for some individuals, but it is less effective for individuals with EGFR mutations.
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Tyrosine Kinase Inhibitors:
Tyrosine kinase inhibitors (TKIs) are also called EGFR inhibitors. These drugs turn off the overactive EGFR, slowing cancer growth in individuals with EGFR mutations. Afatinib, Osimertinib, Gefitinib, Dacomitinib, and Erlotinib.
Still, EGFR inhibitors were ineffective in treating individuals with the exon 20 insertion mutation, and there was no option for this mutation until the FDA approved Amivantamab-vmjw in May 2021, which proved effective. This was the first targeted therapy for individuals with the EGFR exon 20 mutation.
Conclusion
Exon 20 insertion mutations are changes in the EGFR gene responsible for NSCLC lung cancer. Identifying the gene mutation responsible for the disease is essential. This knowledge will help provide an effective treatment. NSCLC cancer caused by exon 20 insertion mutations does not respond well to chemotherapy. Fortunately, targeted therapy can deliver effective treatment. If you or a loved one has been diagnosed with lung cancer or has questions about genetic testing and treatment options, consult an oncologist to get expert medical guidance and personalized advice.
Key Takeaways
- Exon 20 of the EGFR gene, and mutations in this region can lead to non-small cell lung cancer.
- Exon 20 insertion mutations are rare and may not respond well to many common EGFR-targeted therapies.
- New targeted treatments, such as Amivantamab, have improved treatment options for patients with this mutation.
