Bone and Soft Tissue Sarcoma, KIT

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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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KIT is a gene that provides the code for making a protein belonging to the family of receptor tyrosine kinases (RTKs) that are located on the cell surface. RTKs are the first link in a chain that sends signals from the outside of a cell to the parts inside the cell that control different cellular processes, such as how cells grow and divide (proliferate), become able to perform specific tasks (differentiate) or move (migrate). The KIT protein is activated when another protein, called stem cell factor, attaches (binds) to it. The activated KIT protein then activates other proteins inside the cell, leading to activation of a series of signaling pathways.

Mutations in KIT are the most common genetic change associated with gastrointestinal stromal tumors (GISTs). GISTs are found in the gastrointestinal (GI) tract, usually in the stomach or small intestine. In most cases, these mutations are said to be somatic because, instead of coming from a parent and being present in every cell (hereditary), they are acquired during the course of a person's life and are found only in cells that become cancerous. The mutations create a protein that no longer needs binding of the stem cell factor protein to become activated. Therefore, the signaling systems are always turned on. The constant signaling increases proliferation of a certain type of cell (interstitial cells of Cajal [ICCs]), leading to GIST formation.

KIT mutations also are involved in some cases of acute myeloid leukemia (AML), sinonasal natural killer T-cell lymphoma (NKTCL), some types of melanoma and a type of testicular cancer (seminoma).

Source: Genetics Home Reference
The KIT gene (also known as CD117) encodes for a transmembrane receptor that binds the ligand known as stem cell factor. Binding of the ligand leads to KIT heterodimerization and then autophosphorylation through activation of its intrinsic receptor tyrosine kinase activity. These phosphorylation sites serve as docking areas for the assembly of signal transduction complexes that facilitate MAP kinase, PI3K/AKT/mTOR and JAK/STAT pathway activation to promote cellular proliferation and survival. The highest frequency of KIT mutations are found in gastrointestinal stromal tumors (85%) and core binding factor acute myeloid leukemias (46%).

Source: Genetics Home Reference
PubMed ID's
9438854, 15339674, 15948115, 16647948, 17372901, 16908931
Expand Collapse KIT  in Bone and Soft Tissue Sarcoma
Patients with gastrointestinal stromal tumors that carry mutations in exon 11 of the KIT gene are mostly responsive to imatinib therapy, with improvements in recurrence-free survival when compared to placebo. Gastrointestinal stromal tumors with mutations in exon 9 are, however, comparatively less responsive. The presence of mutations in KIT exons other than 9 and 11 can predict for resistance to imatinib treatment.

Mutations at amino acid position D816 in exon 17 of the KIT gene are rare and have been identified as a secondary mutation that occurs in imatinib-resistant tumors. However, these mutations may promote sensitivity to the inhibitor dasatinib.

Patients with gastrointestinal stromal tumors that carry mutations in exon 11 of the KIT gene are mostly responsive to imatinib therapy, with improvements in recurrence-free survival when compared to placebo. Gastrointestinal stromal tumors with mutations in exon 9 are, however, comparatively less responsive. The presence of mutations in KIT exons other than 9 and 11 can predict for resistance to imatinib treatment.

Mutations at amino acid position D816 in exon 17 of the KIT gene are rare and have been identified as a secondary mutation that occurs in imatinib-resistant tumors. However, these mutations may promote sensitivity to the inhibitor dasatinib.

PubMed ID's
21387287, 15365079, 18955451
Expand Collapse No mutation selected
The mutation of a gene provides clinicians with a very detailed look at your cancer. Knowing this information could change the course of your care. To learn how you can find out more about genetic testing please visit http://www.massgeneral.org/cancer/news/faq.aspx or contact the Cancer Center.

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing Results: 1-10 of 27 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 Subjects 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 Subjects 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 27 Per Page:
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