Melanoma, BRAF, V600E (c.1799T>A)

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Expand Collapse Melanoma  - General Description Skin cancer is a malignant tumor that grows in the skin cells and accounts for more than 50 percent of all cancers. There are generally three different types of skin cancer: basal cell carcinoma, squamous cell carcinoma and melanoma.

Basal cell carcinoma and squamous cell carcinoma usually appear on sun-exposed areas of the body. The prognosis for these two types of skin cancer is generally good. Both can often be effectively treated through surgery, with a minority of cases requiring radiation treatment.

Melanoma is the most aggressive form of skin cancer and arises in the cells that produce pigment (color) in the skin. BRAF is the gene that is most frequently mutated in melanoma. The most common BRAF mutations occur at position V600. Vemurafenib is an effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma that has a BRAF V600E mutation. Other melanoma-associated mutations that occur in BRAF also activate the protein abnormally, and can be treated with other targeted agents. Some are sensitive to a combination of BRAF and MEK inhibitors. The combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib was approved by FDA for the treatment of patients with BRAF V600E or V600K mutations. While less frequent, mutations in other genes have been found in melanomas, such as NRAS, MEK, PTEN, TP53, Cyclin D1 (CCND1), CDKN2,and KIT. Mutations in these genes may provide opportunities for enrollment in ongoing clinical trials. Immunology therapies are also being studied in melanoma for patients whose tumors have been tested for specific characteristics. Immuno-therapies are also being tested in combination with targeted therapies in clinical trials at the MGH Cancer Center.

Skin cancer is a malignant tumor that grows in the skin cells and accounts for more than 50 percent of all cancers. There are generally three different types of skin cancer: basal cell carcinoma, squamous cell carcinoma and melanoma.

Basal cell carcinoma and squamous cell carcinoma usually appear on sun-exposed areas of the body. The prognosis for these two types of skin cancer is generally good. Both can often be effectively treated through surgery, with a minority of cases requiring radiation treatment.

Melanoma is the most aggressive form of skin cancer and arises in the cells that produce pigment (color) in the skin. BRAF is the gene that is most frequently mutated in melanoma. The most common BRAF mutations occur at position V600. Vemurafenib is an effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma that has a BRAF V600E mutation. Other melanoma-associated mutations that occur in BRAF also activate the protein abnormally, and can be treated with other targeted agents. Some are sensitive to a combination of BRAF and MEK inhibitors. The combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib was approved by FDA for the treatment of patients with BRAF V600E or V600K mutations. While less frequent, mutations in other genes have been found in melanomas, such as NRAS, MEK, PTEN, TP53, Cyclin D1 (CCND1), CDKN2,and KIT. Mutations in these genes may provide opportunities for enrollment in ongoing clinical trials. Immunology therapies are also being studied in melanoma for patients whose tumors have been tested for specific characteristics. Immuno-therapies are also being tested in combination with targeted therapies in clinical trials at the MGH Cancer Center.

Skin cancer is a malignant tumor that grows in the skin cells and accounts for more than 50 percent of all cancers. There are generally three different types of skin cancer: basal cell carcinoma, squamous cell carcinoma and melanoma.

Basal cell carcinoma and squamous cell carcinoma usually appear on sun-exposed areas of the body. The prognosis for these two types of skin cancer is generally good. Both can often be effectively treated through surgery, with a minority of cases requiring radiation treatment.

Melanoma is the most aggressive form of skin cancer and arises in the cells that produce pigment (color) in the skin. BRAF is the gene that is most frequently mutated in melanoma. The most common BRAF mutations occur at position V600. Vemurafenib is an effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma that has a BRAF V600E mutation. Other melanoma-associated mutations that occur in BRAF also activate the protein abnormally, and can be treated with other targeted agents. Some are sensitive to a combination of BRAF and MEK inhibitors. The combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib was approved by FDA for the treatment of patients with BRAF V600E or V600K mutations. While less frequent, mutations in other genes have been found in melanomas, such as NRAS, MEK, PTEN, TP53, Cyclin D1 (CCND1), CDKN2,and KIT. Mutations in these genes may provide opportunities for enrollment in ongoing clinical trials. Immunology therapies are also being studied in melanoma for patients whose tumors have been tested for specific characteristics. Immuno-therapies are also being tested in combination with targeted therapies in clinical trials at the MGH Cancer Center.

Skin cancer is a malignant tumor that grows in the skin cells and accounts for more than 50 percent of all cancers. There are generally three different types of skin cancer: basal cell carcinoma, squamous cell carcinoma and melanoma.

Basal cell carcinoma and squamous cell carcinoma usually appear on sun-exposed areas of the body. The prognosis for these two types of skin cancer is generally good. Both can often be effectively treated through surgery, with a minority of cases requiring radiation treatment.

Melanoma is the most aggressive form of skin cancer and arises in the cells that produce pigment (color) in the skin. BRAF is the gene that is most frequently mutated in melanoma. The most common BRAF mutations occur at position V600. Vemurafenib is an effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma that has a BRAF V600E mutation. Other melanoma-associated mutations that occur in BRAF also activate the protein abnormally, and can be treated with other targeted agents. Some are sensitive to a combination of BRAF and MEK inhibitors. The combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib was approved by FDA for the treatment of patients with BRAF V600E or V600K mutations. While less frequent, mutations in other genes have been found in melanomas, such as NRAS, MEK, PTEN, TP53, Cyclin D1 (CCND1), CDKN2,and KIT. Mutations in these genes may provide opportunities for enrollment in ongoing clinical trials. Immunology therapies are also being studied in melanoma for patients whose tumors have been tested for specific characteristics. Immuno-therapies are also being tested in combination with targeted therapies in clinical trials at the MGH Cancer Center.

PubMed ID's
21343559, 22798288, 20551065
Expand Collapse BRAF  - General Description
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The BRAF gene encodes a serine/threonine kinase that activates the growth-promoting MAP kinase signaling cascade. BRAF is commonly activated by somatic point mutations in human cancers, most frequently by mutations located within the kinase domain at amino acid positions G466, G469, L597 and V600.

In regards to treatment, the Food and Drug Administration (FDA) approved the BRAF inhibitor, vemurafenib, for the treatment of unresectable or metastatic melanoma patients harboring specifically the BRAF V600E mutation, as detected by an FDA-approved test. In addition, there are a growing number of targeted agents that are being evaluated for the treatment of various BRAF-mutant advanced cancers, including other RAF kinase inhibitors and/or MEK inhibitors. Recently, the combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib was approved by FDA for the treatment of patients with BRAF V600E or V600K mutations.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified the highest incidence of BRAF mutations in thyroid cancer (30-40%), melanoma (20-30%) and colon cancer (10-15%).

To read more about the various BRAF based trials ongoing at the MGH Cancer Center, click on the "disease-gene-mutation" tab on the web page, and select relevant information. Current trials will appear as a ist under the posted information.


Source: Genetics Home Reference
The BRAF gene encodes a serine/threonine kinase that activates the growth-promoting MAP kinase signaling cascade. BRAF is commonly activated by somatic point mutations in human cancers, most frequently by mutations located within the kinase domain at amino acid positions G466, G469, L597 and V600.

In regards to treatment, the Food and Drug Administration (FDA) approved the BRAF inhibitor, vemurafenib, for the treatment of unresectable or metastatic melanoma patients harboring specifically the BRAF V600E mutation, as detected by an FDA-approved test. In addition, there are a growing number of targeted agents that are being evaluated for the treatment of various BRAF-mutant advanced cancers, including other RAF kinase inhibitors and/or MEK inhibitors. Recently, the combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib was approved by FDA for the treatment of patients with BRAF V600E or V600K mutations.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified the highest incidence of BRAF mutations in thyroid cancer (30-40%), melanoma (20-30%) and colon cancer (10-15%).

To read more about the various BRAF based trials ongoing at the MGH Cancer Center, click on the "disease-gene-mutation" tab on the web page, and select relevant information. Current trials will appear as a ist under the posted information.

Source: Genetics Home Reference
PubMed ID's
12068308, 15947100, 20401974, 20425073, 21606968
Expand Collapse V600E (c.1799T>A)  in BRAF
The BRAF V600E mutation arises from a single nucleotide change (c.1799T>A) and results in an amino acid substitution of the valine (V) at position 600 by a glutamic acid (E).
The BRAF V600E mutation arises from a single nucleotide change (c.1799T>A) and results in an amino acid substitution of the valine (V) at position 600 by a glutamic acid (E).

Mutations in the gene encoding BRAF are frequent in melanoma. Mutations at the V600 position, for example V600E occur, often following treatment with first line BRAF inhibitor therapies. This mutation can confer resistance to first line BRAF inhibitor drugs. Mutations can also occur in other regions of the BRAF gene. All result in the production of an abnormal BRAF protein that cannot be regulated normally.

Mutated BRAF is a validated therapeutic target in the treatment of advanced (metastatic) or unresectable (cannot be removed by surgery) melanoma, with several therapies already having received FDA approval for clinical use. The BRAF inhibitors vemurafenib and dabrafenib are FDA-approved for treatment of unresectable or metastatic melanoma in patients whose tumors carry the BRAF V600E mutation (the mutation must have been detected by an FDA-approved test). MEK inhibitors have also been approved by the FDA for the treatment of patients with metastatic or unresectable melanoma whose tumors carry BRAF V600E or V600K gene mutations. Melanomas with other V600 mutations (V600A, V600G, V600G, V600M, V600R)as well as other activating BRAF mutations may also be sensitive to treatment with these inhibitors.

There are a growing number of other targeted agents that are being evaluated for the treatment of BRAF-mutant advanced melanoma. In addition, Immunonology therapies are being studied in combination with targeted therapies in clinical trials at the MGH Cancer Center. (See available trials at the MGH Cancer Center listed below).


Mutations in the gene encoding BRAF are frequent in melanoma. Mutations at the V600 position, for example V600E occur, often following treatment with first line BRAF inhibitor therapies. This mutation can confer resistance to first line BRAF inhibitor drugs. Mutations can also occur in other regions of the BRAF gene. All result in the production of an abnormal BRAF protein that cannot be regulated normally.

Mutated BRAF is a validated therapeutic target in the treatment of advanced (metastatic) or unresectable (cannot be removed by surgery) melanoma, with several therapies already having received FDA approval for clinical use. The BRAF inhibitors vemurafenib and dabrafenib are FDA-approved for treatment of unresectable or metastatic melanoma in patients whose tumors carry the BRAF V600E mutation (the mutation must have been detected by an FDA-approved test). MEK inhibitors have also been approved by the FDA for the treatment of patients with metastatic or unresectable melanoma whose tumors carry BRAF V600E or V600K gene mutations. Melanomas with other V600 mutations (V600A, V600G, V600G, V600M, V600R)as well as other activating BRAF mutations may also be sensitive to treatment with these inhibitors.

There are a growing number of other targeted agents that are being evaluated for the treatment of BRAF-mutant advanced melanoma. In addition, Immunonology therapies are being studied in combination with targeted therapies in clinical trials at the MGH Cancer Center. (See available trials at the MGH Cancer Center listed below).

PubMed ID's
12068308, 20401974, 21343559, 21606968, 20425073, 20551065, 22735384, 22798288, 22663011, 23020132
Our Melanoma Team

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 48 Per Page:
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Protocol # Title Location Status Match
NCT02110355 A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma MGH Open DGM
NCT02428712 A Study of PLX8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors A Study of PLX8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors MGH Open DGM
NCT02967692 A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma MGH Open DGM
NCT01989585 Dabrafenib, Trametinib, and Navitoclax in Treating Patients With BRAF Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery Dabrafenib, Trametinib, and Navitoclax in Treating Patients With BRAF Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery MGH Closed DGM
NCT01989585 Dabrafenib, Trametinib, and Navitoclax in Treating Patients With BRAF Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery Dabrafenib, Trametinib, and Navitoclax in Treating Patients With BRAF Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery MGH Open DGM
NCT03407170 Immunologic Determinants of Response to Pembrolizumab (MK-3475) in Advanced Melanoma (MK-3475-161/KEYNOTE-161) Immunologic Determinants of Response to Pembrolizumab (MK-3475) in Advanced Melanoma (MK-3475-161/KEYNOTE-161) MGH Open DGM
NCT03272464 INCB039110 in Combination With Dabrafenib and Trametinib in Patients With BRAF-mutant Melanoma and Other Solid Tumors. INCB039110 in Combination With Dabrafenib and Trametinib in Patients With BRAF-mutant Melanoma and Other Solid Tumors. MGH Open DGM
NCT02097225 Onalespib, Dabrafenib, and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery Onalespib, Dabrafenib, and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery MGH Open DGM
NCT02961283 Study of ASN003 in Subjects With Advanced Solid Tumors Study of ASN003 in Subjects With Advanced Solid Tumors MGH Open DGM
NCT02857270 A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer MGH Open DG
Trial Status: Showing Results: 1-10 of 48 Per Page:
12345Next »
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