Melanoma, PTEN, K267fs*9 (c.800delA)

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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 PTEN  - General Description
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PTEN is a gene that provides the code for making a protein called phosphatase and tensin homolog (PTEN). Found in almost all tissues in the body, this protein acts as a tumor suppressor. That is, it keeps cells from growing and dividing too fast or in an uncontrolled way. The PTEN protein is part of a signaling pathway that tells cells to stop dividing and triggers their self-destruction (apoptosis). It also may help control how cells move (migration), stick to other cells (adhesion) and protect their genetic information.

Somatic mutations in PTEN are among the most common genetic changes found in human cancers. Instead of coming from a parent and being present in every cell (hereditary), somatic mutations are acquired during the course of a person's life and are found only in cells that become cancerous. PTEN may be the most frequently mutated gene in prostate cancer and endometrial cancer. These mutations usually result in a defective protein that has lost its ability to be a tumor suppressor. Such mutations also are found in certain brain tumors (glioblastomas and astrocytomas) and melanoma of the skin. Loss of PTEN expression is also a common way by which PTEN activity can be reduced and the PI3K pathway can be activated.

Several related conditions caused by inherited mutations in PTEN are grouped together as PTEN hamartoma tumor syndrome. One of these conditions is Cowden syndrome, which is characterized by the growth of many hamartomas and an increased risk of developing breast, thyroid or endometrial cancer. Mutations that cause Cowden syndrome lead to production of a defective PTEN protein that cannot stop cell division or trigger apoptosis, which contributes to the development of hamartomas and cancerous tumors.

Source: Genetics Home Reference
The PTEN gene encodes a lipid phosphatase that antagonizes oncogenic PI3K/AKT signaling via dephosphorylation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) at the cell membrane. Cancer-associated genomic alterations in PTEN result in PTEN inactivation and thus increased activity of the PI3K/AKT pathway. Somatic mutations of PTEN occur in multiple malignancies, including gliomas, melanoma, prostate, endometrial, breast, ovarian, renal and lung cancers. Germline PTEN mutations are associated with inherited hamartoma syndromes, including Cowden syndrome. Loss of PTEN expression is also a common way by which PTEN activity can be reduced and the PI3K pathway can be activated.

Source: Genetics Home Reference
Expand Collapse K267fs*9 (c.800delA)  in PTEN
The PTEN K267 frameshift mutation arises from a single nucleotide deletion (800delA) and results in a truncated protein.
The PTEN K267 frameshift mutation arises from a single nucleotide deletion (800delA) and results in a truncated protein.

PTEN somatic mutations are seen in melanomas harboring BRAF mutations, but not NRAS mutations.

Loss of PTEN expression has been identified in approximately 20% of melanomas. Deletion of the PTEN gene has been associated with resistance to treatment with BRAF inhibitors (such as vemurafenib) in melanoma cell lines that harbor a BRAF mutation. In other preclinical laboratory models, either PI3K, AKT or mTOR inhibitors administered together with a BRAF or MEK inhibitor appears to overcome this drug resistance. Inhibitors of the PI3-kinase subunit p110 beta appear particularly well-suited to tumors with PTEN deletion and are currently being investigated in patients with PTEN deleted melanomas.

PTEN somatic mutations are seen in melanomas harboring BRAF mutations, but not NRAS mutations.

Loss of PTEN expression has been identified in approximately 20% of melanomas. Deletion of the PTEN gene has been associated with resistance to treatment with BRAF inhibitors (such as vemurafenib) in melanoma cell lines that harbor a BRAF mutation. In other preclinical laboratory models, either PI3K, AKT or mTOR inhibitors administered together with a BRAF or MEK inhibitor appears to overcome this drug resistance. Inhibitors of the PI3-kinase subunit p110 beta appear particularly well-suited to tumors with PTEN deletion and are currently being investigated in patients with PTEN deleted melanomas.

PubMed ID's
15009714
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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
NCT02961283 Study of ASN003 in Subjects With Advanced Solid Tumors Study of ASN003 in Subjects With Advanced Solid Tumors MGH Open DG
NCT02637531 A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549 A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549 MGH Open D
NCT03192345 A First-in-human Study of the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR439459 Monotherapy and Combination of SAR439459 and REGN2810 in Patients With Advanced Solid Tumors A First-in-human Study of the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR439459 Monotherapy and Combination of SAR439459 and REGN2810 in Patients With Advanced Solid Tumors MGH Open D
NCT02561234 A Multiple Dose, Dose Escalation Trial of AEB1102 in Patients With Advanced Solid Tumors A Multiple Dose, Dose Escalation Trial of AEB1102 in Patients With Advanced Solid Tumors MGH Open D
NCT02897765 A Personal Cancer Vaccine (NEO-PV-01) w/ Nivolumab for Patients With Melanoma, Lung Cancer or Bladder Cancer A Personal Cancer Vaccine (NEO-PV-01) w/ Nivolumab for Patients With Melanoma, Lung Cancer or Bladder Cancer MGH Open D
NCT02817633 A Phase 1 Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors A Phase 1 Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors MGH Open D
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 D
NCT03148418 A Study in Participants Previously Enrolled in a Genentech− and/or F. Hoffmann-La Roche Ltd-Sponsored Atezolizumab Study (IMbrella A) A Study in Participants Previously Enrolled in a Genentech− and/or F. Hoffmann-La Roche Ltd-Sponsored Atezolizumab Study (IMbrella A) MGH Open D
NCT02880371 A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors MGH Open D
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
Trial Status: Showing Results: 1-10 of 48 Per Page:
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Our Melanoma Team

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