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  • Writer's pictureDr Edin Hamzić

All About The BRAF Gene

Updated: Jan 29, 2023


The complex structure of Braf V600E kinase domain with a novel Braf inhibitor

What is the BRAF gene? What does the BRAF gene do? Is BRAF the same as RAF?


The BRAF, or with the full name B-Raf Proto-Oncogene encodes an enzyme that belongs to the RAF family of serine/threonine kinases. The BRAF g

ene is a B homolog within the family of the three Raf genes (ARAF (A-RAF), BRAF (B-RAF), and c-RAF(or RAF1)) that all encode serine/threonine protein kinases. So besides the B-Raf kinase, there are two additional kinases encoded by the c-RAF (RAF1) and ARAF genes. By the way, RAF stands for Rapidly Accelerated Fibrosarcoma (RAF), and this abbreviation originates from the study that initially described the first RAF gene. The first RAF gene was isolated from the murine retrovirus. This gene can transform rodent fibroblasts into cancerous cell lines; therefore, this gene was named Virus-induced Rapidly Accelerated Fibrosarcoma (V-RAF). Later on, homologs of this gene were identified in the murine and chicken genome; these were c-RAF genes; later on, other homolog versions of RAF genes were identified. So, the BRAF gene is often confused with the RAF term. So, the BRAF gene encodes B-Raf protein, and it is one of the three RAF homologs, the other two being the c-RAF (RAF1) gene, and the A-RAF gene.



Does everyone have the BRAF gene? Is the BRAF gene hereditary?

Everyone has the BRAF gene, and like with all other genes, it is hereditary, meaning you get one version from your mother and another from your father. However, the most common mutations in the BRAF gene are somatic, which means they occur in somatic cells, not reproductive cells. As only the genetic material from reproductive cells is transmitted to progeny, the chance of inheriting the BRAF mutation is meager (but possible and often causes serious problems) as the mutation would need to happen in the reproductive cell itself for it to be transmitted.



Where is the BRAF gene located? How long is the BRAF gene?

The BRAF gene is located on chromosome 7, or more precisely, the BRAF gene can be found on the cytogenetic position 3.4 of the short arm of chromosome 7. The BRAF gene is over 194000 base pairs long.



What does BRAF code for? What is the function of the BRAF gene?

As we mentioned above, the BRAF gene encodes the B-Raf protein, which belongs to the family of the RAF family of serine/threonine kinases. Serine/threonine kinases are enzymes that facilitate the transfer of a phosphate group (the process of phosphorylation).

Now, the term phosphorylation does not tell much to a layman, but the transfer of phosphate groups (phosphorylation) plays a vital role in regulating the MAP kinase/ERK signalling pathway and the MAP kinase/ERK signalling pathway. These pathways are further critical in cell division, cell differentiation, and secretion processes.

The BRAF gene and consequently the protein that it encodes (B-Raf protein) are involved in are: enabling ATP binding, enabling MAP kinase [citation] and MAP kinase kinase kinase activity [citation], and enabling calcium ion binding [citation].

As it goes with genes, in general, 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 BRAF gene, the B-Raf Proto-Oncogene, Serine/Threonine Kinase that is encoded by BRAF genes is involved in the processes of regulating the MAP kinase/ERK pathway, and mutations in the BRAF gene have been associated with the following diseases:

  1. Lung adenocarcinoma

  2. Cardiofaciocutaneous syndrome

  3. Colorectal cancer

  4. Leopard syndrome

  5. Malignant melanoma

  6. Nonsmall cell lung cancer,

  7. Noonan syndrome



What causes BRAF gene mutation? Is BRAF a gain of function mutation?

BRAF gene mutation can be either inherited or caused by environmental factors. The most common mutation that occurs in the BRAF gene is the V600E mutation, where Valine (V) is substituted by glutamic acid (E) at amino acid residue 600. BRAF V600E mutation was found to be a causative agent of over 50% of malignant melanoma cases. As BRAF is a proto-oncogene, the disease-causing mutation is a gain of function mutation.



Is BRAF a tumor suppressor? Is BRAF a biomarker?

BRAF is not a tumor suppressor; it is a proto-oncogene. Mutations in the BRAF gene are associated with more than one disease and more than one type of cancer; it is not a biomarker for diagnosis. However, BRAF is a prognostic biomarker for aggressive tumor growth and a biomarker for predicting the therapeutic response of advanced melanoma.



How do you identify a BRAF mutation? How is BRAF mutation detected? What is the most common BRAF mutation? What does BRAF wild type mean?

Identification of BRAF mutation is made using DNA-based techniques designed for pinpointing changes in the DNA sequence of a gene. The most commonly used method for detecting the BRAF mutation is real-time polymerase chain reaction (RT-PCR), for which a representative test is the Cobas 4800 BRAF V600 test kit. Other techniques include Sanger sequencing and immunohistochemistry. The most common BRAF mutation is V600E, where Valine (V) is substituted by Glutamic acid (E) on amino acid residue 600. BRAF wild type is the non-mutated form of the BRAF gene.



Is the BRAF test a blood test? How common is the BRAF mutation?

In a conventional sense, the BRAF gene test is not a blood test. The reason for this is the fact that testing for this mutation must be performed on a sample of the tumor. Estimation of the BRAF mutation in the general population has not been done to this date. However, there are estimates of how common BRAF mutation is in cancers it was found to be associated with. BRAF mutation is discovered in a large number of melanomas and was found in 80% of melanomas and nevi, 5% of colorectal carcinomas, and 1-3% of lung cancers [citation].


What does BRAF positive mean? What does BRAF negative mutation mean? Is it better to be BRAF positive or negative?

BRAF positive means that the tested sample has the BRAF V600E mutation. BRAF negative mutation means that the tested biopsy sample does not have a BRAF V600E mutation. When it comes to the prognosis of the disease, it is prognostically better to be BRAF negative rather than BRAF positive [citation]. BRAF mutation-positive indicates that a BRAF mutation was detected in the tested biopsy sample.


How long does it take to get BRAF results?

The overall procedure of getting BRAF test results is only a few hours, and results can be obtained the same day.


What does BRAF mean in medical terms? What cancers have BRAF mutations?

BRAF in medical terms is a gene whose mutation is associated with a lot of cancer types and is a strong influencer on the overall survival rate. The mutational status of BRAF can guide medical doctors toward the establishment of proper disease management and treatment plan. Cancers that have BRAF mutations are:

  • lung adenocarcinoma,

  • non-small cell lung cancer,

  • colorectal cancer,

  • malignant melanoma.

How common is BRAF mutation in melanoma? What percentage of melanomas are BRAF positive? How many melanomas have BRAF mutation?

BRAF mutation is very common in melanoma. The incidence of BRAF mutation in melanoma goes up to 80%, and the average is 40-60%.




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