Bone and Soft Tissue Sarcoma, Beta-Catenin (CTNNB1), all mutations

View:
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 Beta-Catenin (CTNNB1)  - General Description
CLICK IMAGE FOR MORE INFORMATION
The CTNNB1 gene encodes a protein called beta-catenin that has several important functions in the cell. These include being involved in cell to cell contacts at adherens junctions, and being involved in the WNT signaling pathway.

The first role beta-catenin is integral to is in participating in cell to cell contacts. Where cells are in contact with one another, beta catenin is part of a complex of proteins that form what are called adherens junctions. Adherens junctions are protein complexes that occur at cell-to-cell junctions and are essential for the formation and maintenance of epithelial cell layers. In this role, beta-catenin functions to anchor the actin cytoskeleton of cells, and to transmit the contact inhibition signal that causes cells to stop dividing once the epithelial layer of cells is complete. Beta catenin also has a role in cell migration.

In a second role, beta-catenin is involved in the Wnt signaling pathway (see graphic above). In the absence of a Wnt signal, beta catenin is normally kept at very low levels within the cell by a destruction complex. This destruction complex includes proteins called GSK-3, APC, and axin, and is responsible for degrading beta catenin. When a Wnt ligand binds to a Wnt receptor on the cell surface, this triggers a signal in the cell that causes the dissociation of the destruction complex, and beta catenin is no longer degraded. Instead, it builds up in the cytoplasm of the cell, and binds to T cell factor (TCF). Beta catenin/TCF translocate into the nucleus, and bind to Wnt target genes that promote growth, including C-Myc and Cyclin D1.

Mutations in the CTNNB1 gene that encodes the beta catenin protein result in the abnormal accumulation of the beta catenin protein in the cell. These and are frequently found in some cancers including colorectal cancer, endometrial and uterine cancers, as well as medulloblastomas. Mutations in CTNNB1/the beta catenin protein also occur in adenocarcinoma of the lung and colorectal cancers, and less frequently in liver cancer, gastric adenocarcinoma, bladder cancer, desmoid tumors, and pilomatrixoma.

Source: TumorPortal.org
The CTNNB1 gene encodes a protein called beta-catenin that has several important functions in the cell. These include being involved in cell to cell contacts at adherens junctions, and being involved in the WNT signaling pathway.

The first role beta-catenin is integral to is in participating in cell to cell contacts. Where cells are in contact with one another, beta catenin is part of a complex of proteins that form what are called adherens junctions. Adherens junctions are protein complexes that occur at cell-to-cell junctions and are essential for the formation and maintenance of epithelial cell layers. In this role, beta-catenin functions to anchor the actin cytoskeleton of cells, and to transmit the contact inhibition signal that causes cells to stop dividing once the epithelial layer of cells is complete. Beta catenin also has a role in cell migration.

In a second role, beta-catenin is involved in the Wnt signaling pathway (see graphic above). In the absence of a Wnt signal, beta catenin is normally kept at very low levels within the cell by a destruction complex. This destruction complex includes proteins called GSK-3, APC, and axin, and is responsible for degrading beta catenin. When a Wnt ligand binds to a Wnt receptor on the cell surface, this triggers a signal in the cell that causes the dissociation of the destruction complex, and beta catenin is no longer degraded. Instead, it builds up in the cytoplasm of the cell, and binds to T cell factor (TCF). Beta catenin/TCF translocate into the nucleus, and bind to Wnt target genes that promote growth, including C-Myc and Cyclin D1.

Mutations in the CTNNB1 gene that encodes the beta catenin protein result in the abnormal accumulation of the beta catenin protein in the cell. These and are frequently found in some cancers including colorectal cancer, endometrial and uterine cancers, as well as medulloblastomas. Mutations in CTNNB1/the beta catenin protein also occur in adenocarcinoma of the lung and colorectal cancers, and less frequently in liver cancer, gastric adenocarcinoma, bladder cancer, desmoid tumors, and pilomatrixoma.

Source: TumorPortal.org
PubMed ID's
19619488, 22682243
Expand Collapse all mutations  in Beta-Catenin (CTNNB1)
Mutations in CTNNB1, the gene that encodes the beta-catenin protein, have been found in many cancers with varying frequencies. Specific mutations T41A, S45A have been studied and are oncogenic; S23R, D32Y, D32G, D32A, D32N, D32H, D32V, S33Y, S33C, S33A, S33F, G34E, G34V, G34A, I35S, H36P, S37F, S37Y, S37C, S37A, S37P, S37T, T41I, T41N, T41P, T41S, P44A, S45F, S45C, S45del, S45P, S45T, S45Y, K335I, W383R, and N387K are likely to be oncogenic, resulting in accumulation of beta catenin in cells which stimulates growth even in the absence of a WNT signal.

Source: TumorPortal.org
Mutations in CTNNB1, the gene that encodes the beta-catenin protein, have been found in many cancers with varying frequencies. Specific mutations T41A, S45A have been studied and are oncogenic; S23R, D32Y, D32G, D32A, D32N, D32H, D32V, S33Y, S33C, S33A, S33F, G34E, G34V, G34A, I35S, H36P, S37F, S37Y, S37C, S37A, S37P, S37T, T41I, T41N, T41P, T41S, P44A, S45F, S45C, S45del, S45P, S45T, S45Y, K335I, W383R, and N387K are likely to be oncogenic, resulting in accumulation of beta catenin in cells which stimulates growth even in the absence of a WNT signal.

Source: TumorPortal.org

Share with your Physican

Print information for your Physician.

Print information

Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing all 10 results Per Page:
Protocol # Title Location Status Match
NCT02601950 A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With INI1-Negative Tumors or Relapsed/Refractory Synovial Sarcoma A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With INI1-Negative Tumors or Relapsed/Refractory Synovial 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
NCT02642016 A Study to Evaluate the Safety and Pharmacokinetics of KTN0158 in Adult Patients With Advanced Solid Tumors A Study to Evaluate the Safety and Pharmacokinetics of KTN0158 in Adult Patients 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
NCT02611024 Pharmacokinetic Study of PM01183 in Combination With Irinotecan in Patients With Selected Solid Tumors Pharmacokinetic Study of PM01183 in Combination With Irinotecan in Patients With Selected Solid Tumors MGH Open D
NCT01858168 Phase I Study of Olaprib and Temozolomide for Ewings Sarcoma Phase I Study of Olaprib and Temozolomide for Ewings Sarcoma MGH Open D
NCT01659203 Proton or Photon RT for Retroperitoneal Sarcomas Proton or Photon RT for Retroperitoneal Sarcomas MGH Open D
NCT02180867 Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Hydrochloride Before Surgery in Treating Patients With Newly Diagnosed Non-Rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Hydrochloride Before Surgery in Treating Patients With Newly Diagnosed Non-Rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery MGH Open D
NCT02576431 Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE) Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE) MGH Open D
NCT02660034 The Safety, Pharmacokinetics and Antitumor Activity of the BGB-A317 in Combination With the BGB-290 in Subjects With Advanced Solid Tumors The Safety, Pharmacokinetics and Antitumor Activity of the BGB-A317 in Combination With the BGB-290 in Subjects With Advanced Solid Tumors 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 10 results Per Page:

Share with your Physican

Print information for your Physician.

Print information