Melanoma, BRAF, V600A (c.1799T>C)

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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 V600A (c.1799T>C)  in BRAF
The BRAF V600A mutation arises from a single nucleotide change (c.1799T>C) and results in an amino acid substitution of the valine (V) at position 600 by an alanine (A).
The BRAF V600A mutation arises from a single nucleotide change (c.1799T>C) and results in an amino acid substitution of the valine (V) at position 600 by an alanine (A).

Mutations in the gene encoding BRAF are frequent in melanoma. Mutations at the V600 position, for example V600A occur, as do mutations in other regions of the 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 V600A occur, as do mutations in other regions of the 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
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing all 5 results Per Page:
Protocol # Title Location Status Match
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 DG
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 DG
NCT02437136 Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in NSCLC With Expansion Cohorts in NSCLC, Melanoma, and Colorectal Cancer Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in NSCLC With Expansion Cohorts in NSCLC, Melanoma, and Colorectal Cancer MGH Open DG
NCT01325441 A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies MGH Open D
NCT02568267 Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) MGH Open D
MGH has many open clinical trials for other cancers not shown on the Targeted Cancer Care website. They can be found on the MassGeneral.org clinical trials search page.

Additional clinical trials may be applicable to your search criteria, but they may not be available at MGH. These clinical trials can typically be found by searching the clinicaltrials.gov website.
Trial Status: Showing all 5 results Per Page:
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