Bone and Soft Tissue Sarcoma, KIT, D816A (c.2447A>C)

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Expand Collapse Bone and Soft Tissue Sarcoma  - General Description This year about 12,000 people in the U.S. will be told by a doctor that they have cancer of the soft tissue. Sarcomas develop more commonly in adults, although certain types of sarcoma are found more typically in children.

Soft tissue sarcomas can form almost anywhere in the body, including cartilage, fat, muscle, fibrous tissue, blood vessels, and other connective or supportive tissues; osteosarcomas develop in bone, liposarcomas form in fat; rhabdomyosarcomas form in muscle; Ewing sarcomas form in bone and soft tissue; Kaposi sarcoma and uterine sarcoma are other types of soft tissue sarcomas. Because there are many types of soft tissue sarcoma, the cell type must be identified before treatment decisions are made. There are ongoing clinical trials using many forms of therapy in specific types of sarcoma.

Source: National Cancer Institute, 2017
This year about 12,000 people in the U.S. will be told by a doctor that they have cancer of the soft tissue. Sarcomas develop more commonly in adults, although certain types of sarcoma are found more typically in children.

Soft tissue sarcomas can form almost anywhere in the body, including cartilage, fat, muscle, fibrous tissue, blood vessels, and other connective or supportive tissues; osteosarcomas develop in bone, liposarcomas form in fat; rhabdomyosarcomas form in muscle; Ewing sarcomas form in bone and soft tissue; Kaposi sarcoma and uterine sarcoma are other types of soft tissue sarcomas. Because there are many types of soft tissue sarcoma, the cell type must be identified before treatment decisions are made. There are ongoing clinical trials using many forms of therapy in specific types of sarcoma.

Source: National Cancer Institute, 2017
This year about 12,000 people in the U.S. will be told by a doctor that they have cancer of the soft tissue. Sarcomas develop more commonly in adults, although certain types of sarcoma are found more typically in children.

Soft tissue sarcomas can form almost anywhere in the body, including cartilage, fat, muscle, fibrous tissue, blood vessels, and other connective or supportive tissues; osteosarcomas develop in bone, liposarcomas form in fat; rhabdomyosarcomas form in muscle; Ewing sarcomas form in bone and soft tissue; Kaposi sarcoma and uterine sarcoma are other types of soft tissue sarcomas. Because there are many types of soft tissue sarcoma, the cell type must be identified before treatment decisions are made. There are ongoing clinical trials using many forms of therapy in specific types of sarcoma.

Source: National Cancer Institute, 2017
This year about 12,000 people in the U.S. will be told by a doctor that they have cancer of the soft tissue. Sarcomas develop more commonly in adults, although certain types of sarcoma are found more typically in children.

Soft tissue sarcomas can form almost anywhere in the body, including cartilage, fat, muscle, fibrous tissue, blood vessels, and other connective or supportive tissues; osteosarcomas develop in bone, liposarcomas form in fat; rhabdomyosarcomas form in muscle; Ewing sarcomas form in bone and soft tissue; Kaposi sarcoma and uterine sarcoma are other types of soft tissue sarcomas. Because there are many types of soft tissue sarcoma, the cell type must be identified before treatment decisions are made. There are ongoing clinical trials using many forms of therapy in specific types of sarcoma.

Source: National Cancer Institute, 2017
Expand Collapse KIT  - General Description
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The KIT gene (also known as CD117) encodes a transmembrane receptor that binds the ligand known as stem cell factor (SCF). Binding of the ligand SCF on the outside of the cell leads to the activation of the KIT receptor tyrosine kinase inside the cell. When tyrosine kinases are activated, they become phosphorylated, meaning they have phosphate added at specific sites on the portion of the receptor that is inside the cell. These phosphorylation sites serve as docking sites for the assembly of signal proteins that then cause the activation of several signal pathways. When KIT is activated, it specifically activates the MAP kinase pathway, the PI3K/AKT/mTOR pathway, and the JAK/STAT pathway. When activated, these signal pathways promote cellular proliferation and survival.

In studies examining the KIT protein in cancers, mutations in KIT have been identified that lead to the production of an altered protein that cannot be regulated normally. Invariably, the mutated KIT protein found in tumors no longer needs SCF ligand binding to the external portion of the receptor to be activated. Instead, mutated KIT stays in a constantly activated state. This constant stimulation of growth and survival signal pathways can leads to the development of cancer. Mutations and other genetic alterations in the gene encoding KIT have been found in several tumor types. Mutations in the KIT protein are frequently found in GastroIntestinal Stromal Tumors (GIST), in some types of Acute Myeloid Leukemia (AML), in melanoma, and less frequently in some other types of tumors. Clinical trials involving KIT inhibitors, as well as KIT inhibitors used in combination with other therapeutic agents are underway at the MGH Cancer Center. Further studies are needed to prevent the growth of tumors containing KIT alterations.
The KIT gene (also known as CD117) encodes a transmembrane receptor that binds the ligand known as stem cell factor (SCF). Binding of the ligand SCF on the outside of the cell leads to the activation of the KIT receptor tyrosine kinase inside the cell. When tyrosine kinases are activated, they become phosphorylated, meaning they have phosphate added at specific sites on the portion of the receptor that is inside the cell. These phosphorylation sites serve as docking sites for the assembly of signal proteins that then cause the activation of several signal pathways. When KIT is activated, it specifically activates the MAP kinase pathway, the PI3K/AKT/mTOR pathway, and the JAK/STAT pathway. When activated, these signal pathways promote cellular proliferation and survival.

In studies examining the KIT protein in cancers, mutations in KIT have been identified that lead to the production of an altered protein that cannot be regulated normally. Invariably, the mutated KIT protein found in tumors no longer needs SCF ligand binding to the external portion of the receptor to be activated. Instead, mutated KIT stays in a constantly activated state. This constant stimulation of growth and survival signal pathways can leads to the development of cancer. Mutations and other genetic alterations in the gene encoding KIT have been found in several tumor types. Mutations in the KIT protein are frequently found in GastroIntestinal Stromal Tumors (GIST), in some types of Acute Myeloid Leukemia (AML), in melanoma, and less frequently in some other types of tumors. Clinical trials involving KIT inhibitors, as well as KIT inhibitors used in combination with other therapeutic agents are underway at the MGH Cancer Center. Further studies are needed to prevent the growth of tumors containing KIT alterations.

PubMed ID's
9438854, 15339674, 15948115, 16647948, 17372901, 16908931
Expand Collapse D816A (c.2447A>C)  in KIT
The KIT D816A mutation arises from a single nucleotide change (c.2447A>C) and results in an amino acid substitution of the aspartic acid (D) at position 816 by an alanine (A).
The KIT D816A mutation arises from a single nucleotide change (c.2447A>C) and results in an amino acid substitution of the aspartic acid (D) at position 816 by an alanine (A).

Mutations at amino acid position D816 in exon 17 of the KIT gene are rare and have been identified in some sarcoma patients as a secondary mutation in tumors. Studies are underway to determine the best therapy for patients with this mutation.

Mutations at amino acid position D816 in exon 17 of the KIT gene are rare and have been identified in some sarcoma patients as a secondary mutation in tumors. Studies are underway to determine the best therapy for patients with this mutation.

PubMed ID's
16397263, 14645423

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 26 Per Page:
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Protocol # Title Location Status Match
NCT03092323 A Randomized Trial of Pembrolizumab & Radiotherapy Versus Radiotherapy in High-Risk Soft Tissue Sarcoma of the Extremity A Randomized Trial of Pembrolizumab & Radiotherapy Versus Radiotherapy in High-Risk Soft Tissue Sarcoma of the Extremity MGH Open D
NCT02659020 A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma MGH Open D
NCT03126591 A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue Sarcoma A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue Sarcoma MGH Open D
NCT00585195 A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer MGH Open D
NCT02748135 A Two-Part Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma A Two-Part Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma MGH Open D
NCT02278250 An Open-Label Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-803/M4344 as a Single Agent and in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors An Open-Label Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-803/M4344 as a Single Agent and in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors 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
NCT02867592 Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors MGH Open D
NCT03002805 CBT-1® in Combination With Doxorubicin in Patients With Metastatic, Unresectable Sarcomas Who Previously Progressed on Doxorubicin CBT-1® in Combination With Doxorubicin in Patients With Metastatic, Unresectable Sarcomas Who Previously Progressed on Doxorubicin MGH Open D
NCT02454972 Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors MGH Open D
Trial Status: Showing Results: 1-10 of 26 Per Page:
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