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  • Writer's pictureDr Edin Hamzić

EZH2 Gene and Cancer: A Comprehensive Overview

Updated: Feb 11, 2023

What is the EZH2 gene? What does the EZH2 gene do?

Enhancer of zeste homolog 2 is an abbreviation for the EZH2 gene. Laible et al. discovered the EZH2 gene while screening for human homologs of E(z) in B-cell-specific cDNA libraries [citation]. As with most the genes, the EZH2 gene also encodes a protein, and in the case of the EZH2 gene, it is a histone-lysine N-methyltransferase enzyme (EZH2 enzyme).

Where is EZH2 found?

The EZH2 gene is located on cytogenetic band 36.1 of the short arm of chromosome 7, and it is roughly 77089 base pairs long.

What is the function of the EZH2 gene?

The EZH2 gene encodes for histone-lysine N-methyltransferase enzyme (EZH2 enzyme), which belongs to histone methyltransferases. Histone methyltransferases facilitate the methylation of histones, and they can suppress the activity of specific genes. Histones are DNA binding proteins. DNA is bundled around histones, giving chromosomes their characteristic shape.

As already mentioned, histone modifications by the EZH2 enzyme can turn off / suppress the activity of specific genes that are essential for normal development. The EZH2 enzyme, specifically, forms a group of polycomb repressive complex-2 that can turn off particular genes involved in cell fate determination.

Where is the EZH2 gene expressed?

The EZH2 gene is expressed mainly in the bone marrow and lymphoid tissues, male tissues, female tissues, and skin. In addition, the EZH2 gene is also expressed in the upper digestive tract, gastrointestinal tract, respiratory system, endocrine tissues, eye, muscle tissues, connective and soft tissue, and brain [citation].

The EZH2 gene and mutations

As it goes with genes, they can have mutations that lead to changes in the protein that they encode which further leads to that given protein to change its function in different ways by being more or less active or inactive. These changes in protein function further lead to cause or can be associated with specific conditions and diseases.

In the case of the EZH2 gene, the EZH2 enzyme that is encoded by EZH2 genes is involved in multiple cellular processes such as B cell differentiation, DNA methylation transition from G1 to G0 cell cycle phase, cell development, cellular response to hydrogen peroxide, cerebellar cortex development, chromatin organization, and remodeling. Consequently, mutations in the EZH2 gene have been associated with the following diseases: Weaver syndrome, prostate cancer, and other cancers.

What is the role of the EZH2 gene in cancer? What cancers are related to the EZH2 gene? Is EZH2 a tumor suppressor?

The EZH2 gene is involved in cell cycle progression, and dysregulation of EZH2 accelerates cell proliferation, promoting survival, and thus resulting in cancer development. Types of cancers related to the EZH2 gene are:

  1. Colorectal cancer

  2. Melanoma [citation]

  3. Breast cancer [citation]

  4. Ovarian cancer [citation]

  5. Prostate cancer [citation]

  6. B-cell lymphoma [citation], and

  7. Lung cancer [citation].

The EZH2 gene is not a tumor suppressor; it acts as an enzyme downregulating the expression of tumor suppressor genes and upregulating oncogenes [citation]. If you want learn more on what are oncogenes check my short blog post on this topic here.

What causes EZH2 mutation? What type of mutations are EZH2 mutations?

EZH2 mutations are predominantly caused by somatic mutations, chromosomal gain or loss, and hypermethylation of promoters as a form of post-translational mechanism [citation].

How do you test for EZH2 mutation? What is cobas EZH2 Mutation Test? Who produces cobas EZH2 Mutation Test? What type of genetic technology is used for cobas EZH2 Mutation Test?

Testing for EZH2 mutation is done using allele-specific real-time polymerase chain reaction, which enables qualitative detection of a single nucleotide change in the EZH2 gene.

The cobas® EZH2 Mutation Test by Roche is a real-time, allele-specific polymerase chain reaction (PCR) test for the qualitative detection of single nucleotide mutations of the EZH2 gene.

The test is done on DNA samples extracted from formalin-fixed paraffin-embedded (FFPE) samples of human follicular lymphoma tumor tissue. The test results identify patients who have follicular lymphoma that has the mutation in the EZH2 gene and can subsequently be targeted with a tazemetostat EZH2 inhibitor.

How does the cobas EZH2 mutation test work? What mutations cobas the EZH2 mutation test check for?

The cobas EZH2 mutation test is a real-time qualitative PCR, and it works by detecting single nucleotides by binding probes with a fluorescent reporter. The probes have sequences complementary to the one expected from the mutated EZH2 gene.

Mutations detected by the EZH2 mutation test are Y646N, Y646F, or Y646X (Y646H, Y646S, or Y646C), A682G, and A692V.

What are the positive and negative results of the cobas EZH2 Mutation Test?

The positive result of the cobas EZH2 Mutation Test is observed when a mutation is detected. This indicates that the tested sample of the follicular lymphoma is positive for the EZH2 mutation.

The negative result of the cobas EZH2 Mutation Test is observed when there is no mutation detected. This indicates that the tested sample does not have the characteristic EZH2 mutations.

What is Tazverik (tazemetostat)? For what do we use Tazverik? What is the mechanism of action of Tazverik?

Tazverik is an EZH2 inhibitor. The other name for Tazverik (Tazemetostat) is Epz6438 or E7438. Adult patients use Tazverik to treat relapsed follicular lymphoma or other types of cancer that are positive for the EZH2 mutation. Tazverik blocks the activity of the EZH2 enzyme, thus inhibiting its function as a histone methyltransferase.

How do you reduce EZH2? What is an EZH2 inhibitor? How does Tazverik reduce EZH2 activity?

It is possible to reduce EZH2 activity using EZH2 inhibitors. EZH2 inhibitor is a drug capable of inhibiting the EZH2 enzyme. One of those inhibitors is Tazverik which targets both wild-type (non-mutated) and mutated forms of EZH2 to induce cell cycle arrest leading to apoptosis of cancer cells. Inhibitors such as Tazverik reduce the EZH2 expression.

What are other EZH2 inhibitors? What is epz011989? What is GSK126? What is gsk343?

We will list some of the most common EZH2 inhibitors:

  1. Epz011989 is a potent orally-available EZH2 inhibitor with a robust in vivo activity [citation].

  2. GSK126 is a potent, highly selective EZH2 methyltransferase inhibitor

  3. Gsk343 is an S-Adenosyl-l-methionine competitive inhibitor of EZH2.


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