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  • Writer's pictureDr Edin Hamzić

🧬 Shortly About The EGFR Gene

Updated: Jan 11

❓What Is the EGFR Gene?

  • The EFGR gene encodes the epidermal growth factor receptor that plays crucial roles in both normal physiological conditions and cancerous conditions [citation]. Epidermal growth factor receptors are involved in the process of the evasion of apoptosis, which leads to cell proliferation, invasion, and metastases, all of which are important for cancer phenotypes.

  • Mutation in the tyrosine kinase domain of the EGFR gene was found in a subset of lung cancers. Lung cancers with an EGFR mutation are highly sensitive to EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib.


🗺️ Where Is the EGFR Gene Located?

  • The EFGR gene is located on chromosome 7p12-13,, and is 200 kb long. Initially, EGFR was isolated from mouse submaxillary glands by Stanley Cohen in 1962 and it was described to accelerate the eruption of incisors and eyelid opening and was originally named tooth-opening factor, but it would be renamed EGFR due to the fact that it stimulated the proliferation of epithelial cells. The existence of a specific binding site for EGF, the EGF receptor (EGFR) would later be confirmed in 1975.


🦀 Is the EGFR Gene a Tumor Suppressor Gene?

  • EGFR gene is not a tumor suppressor gene, and when it mutates, acts as an oncogene for the most part.

🦀 The EGFR Gene and Cancer

  • The EFGR gene mutations are mostly:

    • Various base pair deletions (removal of one nucleotide or even of chromosomes)

    • Substitutions (replacement of one nucleotide with another) and

    • Transversions (in which adenine and guanine get exchanged for cytosine and thymine).

  • Most of these mutations are associated with different forms of non-small cell lung cancer, with one of them related to neonatal inflammatory bowel [citation].

🦀 What Cancers Have EGFR Mutations?

  • The most common EGFR mutations in lung adenocarcinomas are exon 19 deletion and exon 21 L858R mutation [citation].

  • EGFR expression is associated with various types of cancer such as lung, head and neck, colon, pancreas, breast, ovary, bladder and kidney cancer, and glioma [citation]. The EGFR gene is expressed in more than 60% NSCLCs.


👪 Is EGFR Gene Mutation Hereditary?

  • The T790M germline mutation of EGFR are hereditary and lead to a predisposition for lung cancer development [citation]. Risk factors for EGFR mutations include aging, pneumonia, and GERD (gastroesophageal reflux disease) [citation].

🧪 How Is EGFR Mutation Testing Done?

  • EGFR mutations can be tested using the following means: fluorescence in situ hybridization [citation], PCR, DNA fragment analysis [citation], mutant-enriched PCR [citation], and PCR single-strand conformation polymorphism (SSCP) analysis [citation].


➕ What Is EGFR Mutation-Positive? What Does EGFR Positive Mean?

  • In the case of non-small cell lung cancer (NSCLC), being the EGFR positive means that a mutation or damage present in the gene causes it to remain stuck in the “on” position,, which leads to abnormal cell growth [citation]. While the mutation itself has no cure yet,, treatment of EGFR-positive patients with tyrosine kinase inhibitors is effective [citation].


🏢 List of FDA Approved Tests That Targets EGFR Mutations

  • The following four tests are FDA approved for identification of mutations in EGFR based on which suitable cancer treatment can be suggested:

    • Dako EGFR pharmDx Kit

    • therascreen EGFR RGQ PCR Kit

    • cobas EGFR Mutation Test v2 and

    • FoundationOne CDx.


🧪 🧬 What is Dako EGFR pharmDx Kit?

  • The EGFR pharmDxTM test is a qualitative immunohistochemical (IHC) kit that detects the EGFR gene expression in normal and neoplastic tissues routinely fixed for histological evaluation. Actually, the EGFR pharmDxTM specifically detects the EGFR (HER1) protein in EGFR-expressing cells and it is used an aid in identifying colorectal cancer patients eligible for treatment with Erbitux (cetuximab) or VectibixTM (panitumumab).

🧪 🧬 What is therascreen EGFR RGQ PCR Kit?

  • This is a real-time PCR test for the qualitative detection of exon 19 deletions and exon 21 (L858R) substitution mutations of the EGFR gene in DNA obtained from non-small cell lung cancer (NSCLC) tumor tissue. The test is used to select patients with NSCLC for whom Iressa (gefitinib), Gilotrif™ (afatinib) and Vizimpro (dacomitinib) are indicated for use. Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for treating advanced non-small cell lung cancer (NSCLC) with proven efficacy.


🧪 🧬 What is cobas EGFR Mutation Test v2?

  • The cobas® EGFR Mutation Test v2 is a RT-PCR test that identifies 42 mutations in exons 18, 19, 20 and 21 of the epidermal growth factor receptor (EGFR) gene, including the T790M resistance mutation.

  • This test is used to aid in identifying patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations and are suitable for treatment with a tyrosine kinase inhibitor. Also, the test provides two options for extraction of DNA which are from plasma and formalin-fixed paraffin-embedded tissue (FFPET).

  • The test is indicated to be used for detection of patients with NSCLC using tissue sanmples (FFPET) and are suitable for treatment with:

    • Tarceva (erlotinib)

    • Tagrisso (osimertinib)

    • Iressa (gefitinib)

    • Gilotrif (afatinib)

    • Vizimpro (dacomitinib).

  • The test can be used using plasma samples for detection of patients with NSCLC using and are suitable for treatment with:

    • Tarceva (erlotinib)

    • Tagrisso (osimertinib)

    • Iressa (gefitinib).


  • The same test is indicated for detection of with NSCLC patients that have EGFR T790M mutation and are suitable for treatment with Tagrisso (osimertinib).


🧪 🧬 What is FoundationOne CDx Test?

  • FoundationOne CDx tests detects patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations from tissue samples and are suitable for treatment with tyrosine kinase inhibitors (TKI) approved by FDA: Tarceva (erlotinib), Tagrisso (osimertinib), Iressa (gefitinib), Gilotrif (afatinib), Vizimpro (dacomitinib).

  • Also, FoundationOne CDx test can be used for identification of patients with Non-small cell lung cancer that have EGFR exon 20 T790M alterations that are suitable for treatment with Tagrisso (osimertinib).


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