What Does it Mean if Your Cancer Has a BRAF Mutation? (2022)

BRAF mutations are DNA changes in some cancer cells that can be treated with newer targeted therapies.

BRAF mutations are found in roughly half of melanomas. Medications that target these mutations have significantly improved the survival rates of metastatic melanoma. BRAF mutations are also present in some non-small cell lung cancers, colon cancers, and other tumor types.

What Does it Mean if Your Cancer Has a BRAF Mutation? (1)

Genomic testing of tumors can look for DNA alterations and determine if the cancer will respond to drugs targeting mutations.

This article looks at what a BRAF mutation is and its frequency in different types of cancer. It also looks at testing, treatment options, and recent advances.

How BRAF Mutations Work

Cancer begins when a series of gene mutations or other genomic alterations transforms a normal cell into a cancer cell. Some of these mutations, referred to as "driver mutations," code for proteins that drive the growth of the tumor.

You may hear the term "targetable mutation" or "actionable mutation." What this means is that a mutation or other alteration in the cancer cells can be "targeted" by an available drug that may slow or halt the growth of the tumor.

Oncogenes and Tumor Suppressor Genes

Most often, cancer develops after a series of mutations in both oncogenes and tumor suppressor genes occurs.

Proto-oncogenes are normal genes that code for proteins important in stimulating cell growth and division. These genes are primarily active during fetal development in the uterus, and for short periods of time in adults to aid in tissue repair.

When mutated, proto-oncogenes become oncogenes. These genes can be thought of as an accelerator on a car that is stuck in the on position. BRAF is a proto-oncogene that becomes an oncogene when mutated—resulting in the continuous production of proteins that stimulate cell proliferation.

Tumor suppressor genes are genes that code for proteins that function to repair damaged DNA or eliminate cells that can't be repaired. When these genes are damaged, they allow abnormal cells to continue to grow and reproduce. The BRCA genes linked to breast cancer are examples of tumor suppressor genes.

The BRAF Gene

The BRAF gene is a proto-oncogene found on chromosome 7, and becomes an oncogene when mutated. The gene codes for a protein (a serine-threonine kinase) that sends signals from outside of the cell to the nucleus that in turn drives the growth of a cell. Discovered in 2002, the oncogene is now known to be an important driver in more than one type of cancer.

While BRAF is an important "driver" of melanoma, a BRAF mutation alone is not responsible for the development of cancer. (At least one other mutation is needed for cancer to develop.) Alone, the mutation can lead to the development of benign moles.

Hereditary vs. Acquired Gene Mutations

It's important to briefly discuss the difference between acquired (somatic) gene mutations (mutations that are acquired after birth in the process of a cell becoming a cancer cell), and hereditary (germline) mutations, mutations that are inherited from one's parents.

BRAF mutations associated with cancer are almost always acquired mutations. Unlike the BRCA mutations that have received a lot of attention in recent years, these mutations are not inherited from a person's parents and cannot be passed down to children. They are present only in the cancer cells and not all of the cells in the body. Acquired mutations are much more common in oncology.

Hereditary (Germ-Line) vs. Acquired (Somatic) Gene Mutations

Types

There are more than 30 different types of mutations that may occur in the BRAF gene, and the most common types of mutations can vary with the type of cancer.

BRAF V600E and BRAF V600K

With melanoma, BRAF V600 E and BRAF V600K account for roughly 90% of BRAF mutations (with BRAF V600E by far the most common).

Non-V600 BRAF Mutations

With lung adenocarcinoma, around 50% to 80% of BRAF mutations are non-V600 variants. In colorectal cancer, 22% to 30% are non-V600 variants.

BRAF Mutations Classes

The science is in its infancy with regard to evaluating the different types of BRAF mutations with respect to treatment and prognosis.

A 2019 study looked at BRAF mutations in non-small cell lung cancer, separating these into three classes with different clinical characteristics. It could be that in the future, specific therapies will be designed to treat subsets of BRAF mutations rather than BRAF mutations in general.

(Video) How to Approach the Patient With BRAF Mutant Tumor

How BRAF Mutations Drive the Growth of Cancer

The BRAF gene codes for (is a blueprint for) a protein called B-Raf. Mutations in the BRAF gene are referred to as "activating mutations" as the mutation results in continuous production of the protein. The continued presence of the B-Raf proteins, in turn, results in continuous signaling for the cell to divide and grow.

B-Raf proteins are part of a signaling pathway (RAF-MEK-ERK) that affects cell growth in several ways. This pathway:

  • Promotes cell proliferation (growth)
  • Promotes cell survival
  • Aids in differentiation (differentiation is the process by which cells mature such that they have specific functions)
  • Aids in migration (movement of cells)
  • Inhibits apoptosis (cell death or self-destruction)

This pathway is very important in the womb as the embryo develops. When continuously activated in an adult, it can result in uncontrolled growth of cells (cancer).

Part of the difficulty in treating cancer lies in the fact that cancer cells are not just a clone of cells that grows continuously. They have other characteristics, such as the ability to break free and spread, avoid cell death, and more. They are also continuously changing, developing new mutations that may allow them to escape our current treatments.

Cancer Cells vs. Normal Cells: How Are They Different?

Cancers That May Involve BRAF Mutations

At the current time, several different types of cancer have been found to harbor BRAF mutations. However, the frequency, as well as the response to BRAF inhibitors, varies.

BRAF mutations are an example of how cancer treatment is changing. In the past, cancers were usually treated according to type (such as breast cancer or colon cancer treatments). BRAF inhibitors, in contrast, are what are now considered "tumor agnostic" medications.

This means that the drugs may work for different types of cancer (for example, melanoma, lung cancer, and colon cancer). However, the cancer cells must have the same type of mutation responsible for driving the growth of the tumor.

Reading studies about BRAF mutations can be confusing. When the term "BRAF wild-type" or BRAF WT is used to describe a tumor, it refers to a cancer that does not have a BRAF mutation.

Melanoma

BRAF mutations are present in a large number of melanomas, and their discovery has led to treatments that have changed the outlook for some people with metastatic or locally advanced melanoma (stage IIIB or stage IIIC). Present in roughly 40% to 60% of melanomas, around 90% are BRAF V600E mutations, with most of the remaining being BRAF V600K.

BRAF mutations appear to be more common in some people and with some tumors, including:

  • Young people with melanoma
  • Tumors found in areas of the body that do not have chronic sun damage (mucosal tumors, such as anal melanoma, have a high incidence of BRAF mutations)
  • Tumors classified as superficial spreading or nodular

Tumors that are BRAF positive also appear to be more likely to spread to the brain.

Non-Small Cell Lung Cancer (Lung Adenocarcinoma)

BRAF mutations are present in a small number (roughly 3%) of people with the type of non-small cell lung cancer called lung adenocarcinoma. This is the type of lung cancer that is most common in never smokers, women, and young people who develop the disease.

With lung adenocarcinoma, BRAF mutations may be present when the tumor is diagnosed, but are more often found as a resistance mutation. This is a mutation that develops in a cancer that has already been treated with another targeted therapy (such as an EGFR inhibitor).

Resistance mutations allow a tumor that had been previously kept in check with a targeted therapy to bypass the pathway targeted by the drug and begin to grow again.

Colorectal Cancer

BRAF mutations are common in colon cancer, but occur primarily in cancers that are "sporadic" (non-genetic). It is very uncommon for BRAF mutations to be present in hereditary colon cancers, such as those in people who have Lynch syndrome. In this way, the presence of the mutation may provide some information on whether the cancer has a genetic basis or not.

Colon tumors with BRAF mutations are more common:

  • In women
  • In people who are diagnosed at an older age
  • In people who do not have a family history of colon cancer
  • In people with right-sided colon cancer

While treatment addressing BRAF mutations in colon tumors was relatively ineffective in the past, newer triple therapy offers much more promise.

Hairy Cell Leukemia

BRAF mutations are relatively common with hairy cell leukemia. The presence of a BRAF mutation can help distinguish hairy cell leukemia from other B cell lymphomas or leukemias.

Thyroid Cancer

BRAF mutations are present in a large number of anaplastic thyroid cancers (a very aggressive tumor that has been challenging to treat), and up to half of papillary thyroid cancers. BRAF mutations are not found in follicular thyroid cancer, medullary carcinomas, or benign tumors, so the presence of the mutation can help distinguish different types of thyroid cancer.

With papillary thyroid cancer, the presence of a BRAF mutation is associated with a higher risk of recurrence and spread to lymph nodes.

Serous Ovarian Cancer

BRAF mutations are relatively common in people who have serous ovarian cancer. The fact that BRAF inhibitors may be effective for treatment is yet another reason why all women who have ovarian cancer should be tested for mutations in addition to BRCA mutations.

Non-BRCA Gene Mutations Associated with Ovarian Cancer

(Video) BRAF mutation – What does it mean? What are the complications of BRAF Inhibitors?

Others

BRAF mutations have been found in a number of other cancers, although infrequently (usually less than 3%). It's not yet known what the significance of the mutation might be with respect to treatment. Some of these include:

  • Non-Hodgkin's lymphoma
  • Acute lymphoblastic leukemia
  • Biliary tract cancer
  • Stomach cancer, GI stromal tumors
  • Esophageal cancer
  • Ependymoma
  • Glioma
  • Cholangiocarcinoma
  • Langerhans cell histiocytosis
  • Ganglioneuroma

Other Conditions Related to BRAF Mutations

While BRAF mutations associated with cancer are almost always somatic (acquired mutations), both acquired and inherited mutations may be responsible for some non-cancer related conditions, such as cardiofaciocutaneous syndrome, Noonan syndrome, Erdheim Chester disease, and giant melanocytic nevus.

BRAF Mutation Testing

Testing for BRAF mutations is critical both for those who are found to have a BRAF mutation and those who are not. Those who have the mutation may be eligible for a treatment that has a significant chance of controlling the cancer for a period of time.

Testing is also important for those who do not have the mutation. For example, using BRAF inhibitors in melanomas without a BRAF mutation may actually lead to progression of a tumor.

Testing is recommended per guidelines for melanoma, non-small cell lung cancer, colon cancer, serous ovarian cancer, and others.

What Does it Mean if Your Cancer Has a BRAF Mutation? (2)

Methods

Several different methods of testing for BRAF are currently available. DNA sequencing (eg. next-generation sequencing) takes time but is the gold standard. It can detect different types of BRAF mutations, as well as many other alterations that may be treatable. A faster test (PCR) can be done, but only detects V600E mutations.

Tumor Testing vs. Liquid Biopsy

Historically, testing done on a sample of tissue obtained via a biopsy has been the gold standard. Unfortunately, tissue biopsies are invasive and may not always be possible.

In recent years, a simple blood test that looks for fragments of tumor DNA (cell-free DNA) in the blood has offered an additional option for genomic testing. Liquid biopsies have been found to be comparable to tissue biopsies in some cases, though many oncologists believe that the ideal is to do genomic testing on both tissue and blood samples.

Discordance

The concept of discordance is an important one for people living with advanced cancer. Some people may be aware that breast cancer can change. For example, a tumor that was once estrogen receptor positive may become negative (and vice versa) when it progresses or spreads. The same is true with genomic alterations such as BRAF mutations.

For this reason, many oncologists recommend re-testing a tumor if it progresses or spreads (even if next-generation sequencing was done before). There can be discordance within a tumor as well, such that some parts of the tumor have a BRAF mutation and others do not.

A potential advantage of liquid biopsies is that they may detect mutations present in a tumor, but not seen in a specific area that is biopsied.

A common scenario is with lung adenocarcinoma that progresses. Since BRAF commonly develops as a resistance mutation, it may not be present on initial testing but may be present when a tumor progresses.

Cancers continually change and develop new mutations. With melanoma, metastases are more likely to be BRAF positive than a primary tumor.

How Cancer With BRAF Mutation Is Treated

There are several important treatment implications associated with the presence of BRAF mutations. This stresses the importance of testing.

For instance, BRAF-positive tumors are not only treated with targeted therapies, but those tumors may respond differently to other forms of treatment, such as chemotherapy or immunotherapy. The presence of BRAF mutations may also provide information about the prognosis of a tumor. Tumors that harbor BRAF mutations can behave differently clinically.

BRAF Inhibitors

BRAF inhibitors are medications that target the pathways cancer cells use to grow in tumors that harbor BRAF mutations.

Unlike chemotherapy drugs, these medications do not "kill" cancer cells, but rather control the growth of a tumor by interrupting the signaling pathway that leads to cell growth and division. As such, they do not (usually) "cure" a cancer, but can sometimes control the growth of a cancer for a significant period of time.

Combined Therapy

BRAF inhibitors are most often used along with medications that inhibit the growth of a tumor at other points in the signaling pathway (such as MEK inhibitors). Interestingly, adding a MEK inhibitor to a BRAF inhibitor is actually associated with fewer side effects than using a BRAF inhibitor alone. The combination also appears to work for a longer period of time.

Triple Therapy

With both melanoma and colon cancer, combining a BRAF inhibitor and a MEK inhibitor with another medication has shown promise in clinical trials.

BRAF Inhibitors

There are now three BRAF inhibitors that have been approved. These drugs directly attack the protein coded for by the mutated BRAF gene.

  • Zelboraf (vemurafenib): This was the first drug approved in 2011 for BRAF V600E mutations
  • Taflinar (dabrafenib): Taflinar was approved (in combination with Mekinist) in 2013 for both V600 E and V600K mutations
  • Braftovi (encorafenib)

MEK Inhibitors

(Video) BRAF Mutations Across Cancers

  • Mekinist (trametinib)
  • Cotellic (cobimetinib)
  • Mektovi (binimetinib)

Metastatic Melanoma

With metastatic melanoma, using a combination of a BRAF inhibitor and MEK inhibitor has been a "game changer" for many people.

Among those treated, almost two-thirds of people with tumors found to be BRAF positive will respond. Newer combinations (such as the combination of Braftovi and Mektovi) may work even better or result in longer control.

Compared with the previous gold standard (the chemotherapy drug dacarbazine), these targeted therapies can increase both progression-free and overall survival.

Unfortunately, cancers almost always become resistant to these medications after a period of time; usually within a year.

Quandary

There is currently a quandary when it comes to choosing the best treatment for people with metastatic melanoma with BRAF mutations. Targeted therapy has a high chance of working, but only controls the disease for a while.

In contrast, immunotherapy is less likely to work, but in some cases can control the disease for a lengthy period of time. This is something referred to not as a cure, but a "durable response."

Targeted therapy (BRAF plus MEK inhibitors) for metastatic melanoma has a high response rate but lasts, on average, only around a year. Immunotherapy has a lower response rate, but sometimes a much longer duration of action.

Triple Therapy

Clinical trials are in progress evaluating the combination of targeted therapy (BRAF and MEK inhibitors) with immunotherapy drugs known as checkpoint inhibitors (PD-1 and PD-L1 inhibitors).

These include a few promising studies published in June of 2019 that suggest that, for at least some people, the combination may result in a longer response:

  • A combination of Taflinar and Mekinist plus Keytruda (pembrolizumab)
  • A combination of Zelboraf and Cotellic plus Tecentriq (atezolizumab)

Stage III Melanoma

A combination of a BRAF inhibitor and MEK inhibitor may also be used in people with locally advanced melanoma (such as stage IIIB and stage IIIC) to reduce the risk of recurrence (adjuvant therapy).

Adjuvant Therapy for Melanoma

Lung Cancer

A combination of the BRAF inhibitor Taflinar and the MEK inhibitor Mekinist is approved for treating non-small cell lung cancer with a BRAF V600E mutation, with a response rate of 64% in studies.

Guidelines also recommend avoiding immunotherapy (Keytruda) first-line in people with BRAF mutations, even if PD-L1 levels are high since people with BRAF mutations appear less likely to respond.

Colorectal Cancer

A large number of non-hereditary colon cancers have BRAF mutations, but studies using a combination of BRAF and MEK inhibitors showed a low response rate (roughly 5% with BRAF inhibition alone and 12% with the combination).

In the past, it was thought that the presence of a BRAF mutation might make a colon cancer unlikely to respond to an EGFR inhibitor, but this appears to depend on other genetic changes in the tumor. With colon cancer, tumors that have a BRAF mutation but not a KRAS mutation may not respond well to EGFR inhibitors such as cetuximab or panitumumab.

BRAF + MEK + EGFR Inhibitors

A 2019 study found that using triple therapy with the BRAF inhibitor Mektovi, the MEK inhibitor Braftovi, and the EGFR inhibitor Erbitux (cetuximab) resulted in a higher response rate and significantly longer survival among people with a BRAF V600E mutation.

Resistance

Unfortunately, most tumors become resistant to these targeted therapies in time. Research is in place evaluating the resistance mutations that develop with hope that further targets can be identified and treated when resistance occurs.

A Word From Verywell

The science surrounding BRAF mutations is young, though already approvals are present that can extend both length and quality of life for some people who have tumors with the mutations.

Not only does genomic testing allow more people to obtain effective treatments, but doing so is advancing our understanding of the natural history of cancer. That's important as new therapies are developed to combat the disease.

Since the science is advancing so rapidly, however, it is hard for any physician to stay abreast of all of the changes with all cancers. Learning about your disease, getting a second (or third opinion), questioning potential clinical trials, and advocating for yourself are all important in receiving the best care possible for your cancer.

Frequently Asked Questions

  • What is the function of the BRAF gene?

    The BRAF gene provides instructions to the protein that manages cell growth. The genes are usually active when a baby is growing during pregnancy and in adults to help with tissue repair.

  • Does everyone have the BRAF gene?

    Yes. The BRAF gene, found on chromosome 7, is responsible for cell growth. However, not everyone has a mutation of the BRAF gene that contributes to cancer development.

  • What does being BRAF mutation-positive mean?

    "BRAF positive" means that your tumor has a mutation in the BRAF gene. This gene controls a protein that stimulates cell growth. When there's a mutation, it causes the continuous production of this protein, which can lead to unchecked cell growth or cancer.

  • Can being BRAF positive be a good thing?

    Knowing your status can help ensure that your healthcare provider is providing the right treatment. If you have a BRAF mutation, you may be eligible for certain targeted treatments, such as BRAF inhibitors, which may help improve survival rates.

  • Are you born with a BRAF mutation?

    It's possible, but not likely. Usually, a BRAF mutation happens later in life from something in the environment or a mistake your body makes during cell division. In very rare cases, BRAF mutations can be inherited, causing serious health problems.

  • Can BRAF mutations disappear?

    No, they can't go away, but treatment may help with managing their effects. With a tumor related to a BRAF mutation, your oncologist can use targeted treatments that may temporarily stop the mechanism causing tumor growth.

(Video) How to approach the patient with a BRAF mutant tumor

FAQs

What does BRAF mutation positive mean? ›

"BRAF positive" means that your tumor has a mutation in the BRAF gene. This gene controls a protein that stimulates cell growth. When there's a mutation, it causes the continuous production of this protein, which can lead to unchecked cell growth or cancer.

Is it better to have BRAF positive or negative? ›

We have demonstrated that BRAF positive patients receiving targeted treatment have significantly better survival than their BRAF negative counterparts.

What does having the BRAF gene mean? ›

It's known as an oncogene. An oncogene works like a gas pedal on a car. Normally, an oncogene turns on cell growth as needed. But if you have a BRAF mutation, it's like the gas pedal is stuck down, and the gene can't stop cells from growing. Uncontrolled cell growth can lead to cancer.

What is the most common BRAF mutation? ›

More than 97% of BRAF mutations are located in codon 600 of the BRAF gene. The most common mutation (in up to 90% of cases) is the result of a transversion of T to A at nucleotide 1799 (T1799A), which results in a substitution of valine (V) for glutamic acid (E) at position 600.

Is BRAF positive good? ›

Getting a positive test for the BRAF V600 tumor mutation is certainly good news for a newly diagnosed melanoma patient. This is because some targeted drugs work very well against such tumors, which account for about 50% of melanomas.

What does BRAF mean in medical terms? ›

Definition of BRAF

BRAF (v-raf murine sarcoma viral oncogene homolog B1) is a serine/threonine protein kinase that plays a critical role in the RAS-RAF-MEK-ERK mitogen activated protein kinase (MAPK) cell signalling pathway.

What cancers are BRAF mutations? ›

BRAF mutation is seen in melanoma, papillary thyroid carcinoma (including papillary thyroid carcinoma arising from ovarian teratoma), ovarian serous tumours, colorectal carcinoma, gliomas, hepatobiliary carcinomas and hairy cell leukaemia.

What is the difference between BRAF positive and BRAF negative? ›

If you have changes in the BRAF gene, doctors describe your melanoma as BRAF positive. If you don't have changes, then your melanoma is BRAF negative. Knowing this can help your doctor make decisions about whether it would be helpful to give you targeted cancer drugs.

Does everyone have a BRAF gene? ›

Everyone Has the BRAF Gene

BRAF is a gene that locks down a specific protein called B-Raf. This protein helps send signals inside your cells that are related to cell growth. Everyone has this gene, and when it's working properly, it's an important part of how cells operate.

In which tissues are BRAF mutations commonly found? ›

This mutation has frequently been found in cancers of the colon and rectum, ovary, and thyroid gland. Several other somatic mutations in the BRAF gene have also been associated with cancer.

What kind of protein is BRAF? ›

BRAF protein is a serine-threonine kinase that is encoded on chromosome 7q34. It is an important signal transduction molecule that mediates signals from RAS to MEK, ultimately promoting cell proliferation and mobility.

What is BRAF targeted therapy? ›

BRAF inhibitors

Vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi) are drugs that attack the BRAF protein directly. These drugs can shrink or slow the growth of tumors in some people whose melanoma has spread or can't be removed completely.

What do BRAF mutations do? ›

What is a BRAF mutation? A BRAF mutation is a spontaneous change in the BRAF gene that makes it work incorrectly. A mutation causes the gene to turn on the protein and keep it on, which means certain cells get ongoing signals to keep dividing and no instructions on when to stop. This can lead to development of a tumor.

How many BRAF mutations are there? ›

At least 49 BRAF mutations have been identified in people with this disorder. These mutations change single protein building blocks (amino acids) in the BRAF protein.

Where is the BRAF gene found? ›

The BRAF gene is located on the long arm of chromosome 7 (7q34) and codes for the serine/threonine protein kinase, B-Raf. B-Raf is a member of the Raf kinase family and is a downstream target of RAS, playing a pivotal role in the MAPK/ERK signaling pathway.

What is the best first line treatment for a patient with BRAF positive metastatic melanoma who doesn't like taking a lot of pills? ›

ASCO recommends dabrafenib plus trametinib as an option to treat stage III melanoma with a BRAF mutation after surgery. For unresectable or metastatic melanoma with a BRAF mutation, ASCO recommends dabrafenib plus trametinib, encorafenib plus binimetinib, or vemurafenib plus cobimetinib as options.

How successful is immunotherapy for melanoma? ›

In a small study published in the Journal of Clinical Oncology, scientists reported a 3-year overall survival rate of 63 percent among 94 patients treated with this combination of drugs.

What is the survival rate of stage 4 melanoma? ›

Researchers are also working every day to improve the durability of response and increase the number of people who benefit from treatment. The 5-year survival rate as of 2018 for distant metastatic (Stage IV) melanoma is 22.5%. Learn more about melanoma survival rates.

How is BRAF mutation detected? ›

The most commonly used technique to identify BRAF mutation is real-time polymerase chain reaction (PCR). A more comprehensive evaluation of BRAF genotypes can be accomplished using DNA sequencing methods, including traditional Sanger sequencing or newer methods, such as pyrosequencing.

Is BRAF a biomarker? ›

The BRAF mutation is also a predictive biomarker, which means it predicts that your tumor is unlikely to respond to treatment with EGFR inhibitors when given alone or in combination with chemotherapy.

When was BRAF mutation discovered? ›

The 2002 discovery of activating mutations in the serine/threonine kinase BRAF (v-raf murine sarcoma viral oncogene homolog B1) in approximately 50% of all melanomas kick-started a targeted therapy “arms race” which in under 10 years led to the FDA-approval of the BRAF inhibitor vemurafenib1,2.

How do BRAF inhibitors work? ›

The BRAF inhibitors vemurafenib, dabrafenib and encorafenib are used in the treatment of patients with BRAF-mutant melanoma. They selectively target BRAF kinase and thus interfere with the mitogen-activated protein kinase (MAPK) signalling pathway that regulates the proliferation and survival of melanoma cells.

What gene is mutated in melanoma? ›

To date, 2 genes have been primarily linked to familial melanoma; they are called CDKN2A and CDK4. A mutation (alteration) in either of these genes gives a person an increased risk of melanoma.

What is BRAF mutation in hairy cell leukemia? ›

A mutation in the RAF gene, especially in BRAF protein, leads to an increased stimulation of this cascade, causing uncontrolled cell division and development of malignancy. Several mutations have been observed in the gene coding for this protein in a variety of human malignancies, including hairy cell leukemia (HCL).

What is BRAF V600E negative? ›

BRAF V600E mutation analysis may be a useful adjunct technique for confirming the diagnosis of papillary thyroid carcinoma. However, the false-negative rate of BRAF mutation testing with FNAC for thyroid nodules is increased in cases of old age, indeterminate FNAC pathology results, and certain PTC subtypes.

What percentage of melanoma is BRAF positive? ›

It is estimated that BRAF mutation is present in approximately 50-60% of cutaneous melanomas.

How does BRAF mutation cause melanoma? ›

A BRAF mutation is a change in a BRAF gene. That change in the gene can lead to an alteration in a protein that regulates cell growth that could allow the melanoma to grow more aggressively. Approximately half of melanomas carry this mutation and are referred to as mutated, or BRAF positive.

How common is BRAF mutation in melanoma? ›

Identification of the BRAF V600 mutation and development of BRAF targeting drugs have radically changed clinical practice and outcomes of advanced or metastatic melanoma. Activating BRAF mutation has been estimated to occur in approximately 50% of cases of cutaneous melanoma.

What is an oncogenic mutation? ›

(ON-koh-jeen) A mutated (changed) form of a type of gene called a proto-oncogene, which is involved in normal cell growth and division. When a proto-oncogene is changed so that too many copies are made or it becomes more active than normal, it is called an oncogene.

What are the four types of melanoma? ›

There are 4 main types of melanoma skin cancer – superficial spreading, nodular, lentigo maligna and acral lentiginous.

What type of mutation is BRAF V600E? ›

BRAF V600E is a point mutation (substitution of a thymine with adenine at position 1799 on exon 15) that results in the change of amino acid 600 from valine (V) to glutamate (E).

Can Dabrafenib cure melanoma? ›

Two such drugs, dabrafenib (Tafinlar) and trametinib (Mekinist), shrink tumors and help patients with advanced melanoma live longer. Through clinical trials, cancer researchers have found that combining dabrafenib and trametinib can treat advanced melanoma more effectively than either medication on its own.

What does KRAS stand for? ›

The presence of these mutations may indicate that certain drugs will not be effective in treating the cancer. KRAS is a short name for the gene Kirsten rat sarcoma viral oncogene homolog. It is one of a group of genes involved in a pathway called the epidermal growth factor receptor (EGFR) pathway.

How do you pronounce BRAF mutation? ›

Pronounce Medical Words ― BRAF V600E Mutation - YouTube

How is BRAF testing done? ›

Sampling Methods. BRAF testing can be done on a tumor tissue sample, via a blood test (liquid biopsy), or both, though tumor tissue remains the "gold standard." BRAF testing is most often done on a sample of tissue taken during a biopsy or removal of a tumor.

How many amino acids are in BRAF? ›

BRAF protein has 766 amino acids and is composed of three main domains. The most important catalytic domain that phosphorylates consensus substrates is residues 457–717, conserved region 3.

How long does targeted therapy last? ›

The targeted therapy drug dose often needs to be reduced when a person has severe skin changes. Expect to see your doctor often during this time. If the rash doesn't get better within about 2 weeks, the targeted drug is often stopped until the skin changes improve.

How long do you stay on immunotherapy for melanoma? ›

People with melanoma are recommended to take an immune checkpoint inhibitor for 12 months, he explained. But in clinical practice, some patients and their doctors decide to stop the therapy a few months earlier if the patient is in remission and has a mild, but bothersome side effect.

What is BRAF wild type? ›

Wild Type: This term describes genes that have no mutation and are normal. For example, some people have melanoma with mutations in BRAF, while others have so-called wild type BRAF melanoma, meaning there's no known mutation present.

Is BRAF mutation curable? ›

As such, they do not (usually) "cure" a cancer, but can sometimes control the growth of a cancer for a significant period of time. BRAF inhibitors are most often used along with medications that inhibit the growth of a tumor at other points in the signaling pathway (such as MEK inhibitors).

What is BRAF V600E positive? ›

BRAF V600E mutation is primarily present in conventional papillary thyroid cancer. It is associated with an aggressive tumor phenotype and higher risk of recurrent and persistent disease in patients with conventional papillary thyroid cancer.

How do you test a BRAF V600E? ›

How the test is performed: BRAF V600E genetic mutations can be detected in tissue samples. Your health care provider will send a tissue sample to a lab for the test. If you've had a biopsy done before, ask your health care provider if your tissue is still available for BRAF V600E biomarker testing.

What does the BRAF gene encode? ›

The BRAF gene encodes for a serine/threonine protein kinase that participates in the MAPK/ERK signalling pathway and plays a vital role in cancers and developmental syndromes (RASopathies).

What is KIAA1549 BRAF fusion? ›

The KIAA1549-BRAF fusion is increasingly used as a diagnostic marker to aid neuropathologic diagnosis in low-grade gliomas because of its high frequency in these tumors, particularly PAs, and its absence in high-grade tumors such as anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV) (15).

What is BRAF short for? ›

BRAF is a human gene that encodes a protein called B-Raf. The gene is also referred to as proto-oncogene B-Raf and v-Raf murine sarcoma viral oncogene homolog B, while the protein is more formally known as serine/threonine-protein kinase B-Raf.

Is there a genetic test for melanoma? ›

The genetic test for melanoma can tell you whether you have a mutation (change) in a gene that gives you an increased risk of developing melanoma. These mutations are passed down in the family tree. If you carry one of these mutations, your lifetime risk of getting melanoma ranges from 60% to 90%.

What cancers are BRAF mutations? ›

BRAF mutation is seen in melanoma, papillary thyroid carcinoma (including papillary thyroid carcinoma arising from ovarian teratoma), ovarian serous tumours, colorectal carcinoma, gliomas, hepatobiliary carcinomas and hairy cell leukaemia.

What is the difference between BRAF positive and BRAF negative? ›

If you have changes in the BRAF gene, doctors describe your melanoma as BRAF positive. If you don't have changes, then your melanoma is BRAF negative. Knowing this can help your doctor make decisions about whether it would be helpful to give you targeted cancer drugs.

In which tissues are BRAF mutations commonly found? ›

This mutation has frequently been found in cancers of the colon and rectum, ovary, and thyroid gland. Several other somatic mutations in the BRAF gene have also been associated with cancer.

How do you know if you have a BRAF mutation? ›

A BRAF Mutation Is Determined From a Biopsy

DNA can also be collected from a sample of cells, using a cheek swab. But the BRAF mutation can't be pinpointed with any of these methods. Instead, it has to be done on a melanoma tumor tissue sample, which means you would need a biopsy.

What do BRAF mutations do? ›

What is a BRAF mutation? A BRAF mutation is a spontaneous change in the BRAF gene that makes it work incorrectly. A mutation causes the gene to turn on the protein and keep it on, which means certain cells get ongoing signals to keep dividing and no instructions on when to stop. This can lead to development of a tumor.

How many BRAF mutations are there? ›

At least 49 BRAF mutations have been identified in people with this disorder. These mutations change single protein building blocks (amino acids) in the BRAF protein.

What is BRAF targeted therapy? ›

BRAF inhibitors

Vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi) are drugs that attack the BRAF protein directly. These drugs can shrink or slow the growth of tumors in some people whose melanoma has spread or can't be removed completely.

What is the best first line treatment for a patient with BRAF positive metastatic melanoma who doesn't like taking a lot of pills? ›

ASCO recommends dabrafenib plus trametinib as an option to treat stage III melanoma with a BRAF mutation after surgery. For unresectable or metastatic melanoma with a BRAF mutation, ASCO recommends dabrafenib plus trametinib, encorafenib plus binimetinib, or vemurafenib plus cobimetinib as options.

What is BRAF V600E negative? ›

BRAF V600E mutation analysis may be a useful adjunct technique for confirming the diagnosis of papillary thyroid carcinoma. However, the false-negative rate of BRAF mutation testing with FNAC for thyroid nodules is increased in cases of old age, indeterminate FNAC pathology results, and certain PTC subtypes.

How successful is immunotherapy for melanoma? ›

In a small study published in the Journal of Clinical Oncology, scientists reported a 3-year overall survival rate of 63 percent among 94 patients treated with this combination of drugs.

What type of protein is BRAF? ›

BRAF protein is a serine-threonine kinase that is encoded on chromosome 7q34. It is an important signal transduction molecule that mediates signals from RAS to MEK, ultimately promoting cell proliferation and mobility.

When was BRAF gene discovered? ›

The 2002 discovery of activating mutations in the serine/threonine kinase BRAF (v-raf murine sarcoma viral oncogene homolog B1) in approximately 50% of all melanomas kick-started a targeted therapy “arms race” which in under 10 years led to the FDA-approval of the BRAF inhibitor vemurafenib1,2.

How do BRAF inhibitors work? ›

The BRAF inhibitors vemurafenib, dabrafenib and encorafenib are used in the treatment of patients with BRAF-mutant melanoma. They selectively target BRAF kinase and thus interfere with the mitogen-activated protein kinase (MAPK) signalling pathway that regulates the proliferation and survival of melanoma cells.

What percentage of melanomas are BRAF positive? ›

BRAF mutations are found in about 40–60% of melanomas, with about 80% occurring as a V600E mutation, 5–30% as V600K mutations, and the rest other rare mutations [21,22,23]. BRAF mutation has been associated as a poor prognostic factor in other cancer types, for example in papillary thyroid cancer [24].

How common is BRAF mutation in melanoma? ›

Identification of the BRAF V600 mutation and development of BRAF targeting drugs have radically changed clinical practice and outcomes of advanced or metastatic melanoma. Activating BRAF mutation has been estimated to occur in approximately 50% of cases of cutaneous melanoma.

How do you test a BRAF V600E? ›

How the test is performed: BRAF V600E genetic mutations can be detected in tissue samples. Your health care provider will send a tissue sample to a lab for the test. If you've had a biopsy done before, ask your health care provider if your tissue is still available for BRAF V600E biomarker testing.

Videos

1. BRAF Mutations in Colorectal Cancer
(OncLiveTV)
2. What is a BRAF-V600E mutation?
(American Lung Association)
3. BRAF in Melanoma Explained
(AIMatMelanoma)
4. BRAF mutated melanoma: targeted or immunotherapy?
(VJOncology)
5. BRAF mutation
(Shomu's Biology)
6. Role of BRAF mutation in the treatment for melanoma
(VJOncology)

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