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

View:
Expand Collapse Bone and Soft Tissue Sarcoma  - General Description This year about 11,000 people in the U.S. will be told by a doctor that they have cancer of the soft tissue. Half of these patients will be at least 58 years old. Among the many types of soft tissue sarcoma, the more common ones are gastrointestinal stromal tumors (GIST), Kaposi sarcoma and uterine sarcoma.

Soft tissue sarcomas can form almost anywhere in the body, including muscles, tendons, fat, blood vessels, lymph vessels, nerves and tissues around joints. In adults, they are most common in the legs and arms (about 50% of all cases), the trunk (about 30% of all cases) and the head and neck (about 10% of cases). Based on the type of soft tissue in which the cancer began, each sarcoma appears different under the microscope.

GIST can occur anywhere along the gastrointestinal tract, including the stomach (about 60% of all cases), small intestine (about 30% of all cases), and large intestine (colon). The FDA has approved the targeted therapies imatinib (Gleevec) and sunitinib (Sutent) in the treatment of certain kinds of GIST.

Kaposi sarcoma causes abnormal tissue (lesions) to grow in the skin; mucous membranes lining the mouth, nose, and throat; lymph nodes; and other organs. Kaposi sarcoma differs from other cancers in that these lesions may begin in more than one place in the body at the same time.

Uterine sarcoma is a rare cancer that forms in the muscles of the uterus or tissues that support the uterus, a hollow organ in the pelvis where a baby (fetus) develops. Uterine sarcoma is different from endometrial cancer, which begins in the lining of the uterus known as the endometrium.

Soft tissue sarcoma (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the bloodstream and go to other places in the body. In these distant places, the cancer cells cause secondary tumors to grow.

To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a node near the primary tumor and a pathologist looks at it through a microscope to see if cancer cells are present. Several kinds of imaging can also be performed to determine if the cancer has spread. These include chest x-rays, MRI, bone scans, CT scans and PET scans.

Despite significant improvements in the treatment of sarcoma and soft tissue tumors, novel therapies and treatment strategies are needed.

Source: National Cancer Institute, 2012
Sarcomas are a heterogenous group of malignancies derived from mesenchymal tissue. There are more than 50 subtypes of sarcomas that can arise from virtually all sites of the human body. The two most common types of soft tissue sarcoma are tumors that differentiate into fat-like cells (liposarcoma) and smooth muscle-like cells (leiomyosarcoma). Many sarcomas are defined by chromosomal translocations that underlie its tumorigenesis, but these are generally not known to be heritable diseases. The risk of sporadic soft tissue sarcomas is increased by prior radiation therapy and, in the case of lymphangiosarcoma, by chronic lymphedema. The chemicals Thorotrast, vinyl chloride and arsenic are also established carcinogens for hepatic angiosarcomas.

Soft tissue sarcomas occur with greater frequency in patients with the following inherited syndromes:

- Nevoid basal cell carcinoma syndrome (Gorlin syndrome: PTCH1 gene mutation)
- Gardner syndrome (APC mutation).
- Li-Fraumeni syndrome (TP53 mutation)
- Tuberous sclerosis (Bourneville disease: TSC1 or TSC2 mutation)
- von Recklinghausen disease (neurofibromatosis type 1: NF1 mutation)
- Werner syndrome (adult progeria: WRN mutation)

Source: National Cancer Institute, 2012
This year about 11,000 people in the U.S. will be told by a doctor that they have cancer of the soft tissue. Half of these patients will be at least 58 years old. Among the many types of soft tissue sarcoma, the more common ones are gastrointestinal stromal tumors (GIST), Kaposi sarcoma and uterine sarcoma.

Soft tissue sarcomas can form almost anywhere in the body, including muscles, tendons, fat, blood vessels, lymph vessels, nerves and tissues around joints. In adults, they are most common in the legs and arms (about 50% of all cases), the trunk (about 30% of all cases) and the head and neck (about 10% of cases). Based on the type of soft tissue in which the cancer began, each sarcoma appears different under the microscope.

GIST can occur anywhere along the gastrointestinal tract, including the stomach (about 60% of all cases), small intestine (about 30% of all cases), and large intestine (colon). The FDA has approved the targeted therapies imatinib (Gleevec) and sunitinib (Sutent) in the treatment of certain kinds of GIST.

Kaposi sarcoma causes abnormal tissue (lesions) to grow in the skin; mucous membranes lining the mouth, nose, and throat; lymph nodes; and other organs. Kaposi sarcoma differs from other cancers in that these lesions may begin in more than one place in the body at the same time.

Uterine sarcoma is a rare cancer that forms in the muscles of the uterus or tissues that support the uterus, a hollow organ in the pelvis where a baby (fetus) develops. Uterine sarcoma is different from endometrial cancer, which begins in the lining of the uterus known as the endometrium.

Soft tissue sarcoma (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the bloodstream and go to other places in the body. In these distant places, the cancer cells cause secondary tumors to grow.

To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a node near the primary tumor and a pathologist looks at it through a microscope to see if cancer cells are present. Several kinds of imaging can also be performed to determine if the cancer has spread. These include chest x-rays, MRI, bone scans, CT scans and PET scans.

Despite significant improvements in the treatment of sarcoma and soft tissue tumors, novel therapies and treatment strategies are needed.

Source: National Cancer Institute, 2012
Sarcomas are a heterogenous group of malignancies derived from mesenchymal tissue. There are more than 50 subtypes of sarcomas that can arise from virtually all sites of the human body. The two most common types of soft tissue sarcoma are tumors that differentiate into fat-like cells (liposarcoma) and smooth muscle-like cells (leiomyosarcoma). Many sarcomas are defined by chromosomal translocations that underlie its tumorigenesis, but these are generally not known to be heritable diseases. The risk of sporadic soft tissue sarcomas is increased by prior radiation therapy and, in the case of lymphangiosarcoma, by chronic lymphedema. The chemicals Thorotrast, vinyl chloride and arsenic are also established carcinogens for hepatic angiosarcomas.

Soft tissue sarcomas occur with greater frequency in patients with the following inherited syndromes:

- Nevoid basal cell carcinoma syndrome (Gorlin syndrome: PTCH1 gene mutation)
- Gardner syndrome (APC mutation).
- Li-Fraumeni syndrome (TP53 mutation)
- Tuberous sclerosis (Bourneville disease: TSC1 or TSC2 mutation)
- von Recklinghausen disease (neurofibromatosis type 1: NF1 mutation)
- Werner syndrome (adult progeria: WRN mutation)

Source: National Cancer Institute, 2012
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 Beta-Catenin (CTNNB1)  in Bone and Soft Tissue Sarcoma
CTNNB1 mutations are highly common in desmoid fibromatosis. This non-metastatic neoplasm is rare in the general population but common in patients with familial cancer predisposition conditions known as familial adenomatous polyposis (FAP) or Gardner syndrome. Within fibromatosis/desmoid tumors, specific S45F mutations in CTNNB1 are associated with a worse 5-year recurrence-free survival compared to tumors with other or no CTNNB1 mutations. In addition, increased local recurrence has been associated with the S45F mutation in this neoplasm.

A single study has identified mutations in CTNNB1 (T41A, S45F and S45P) in the sporadic desmoid tumors of children, which was not associated with familial adenomatous polyposis.

CTNNB1 mutations are highly common in desmoid fibromatosis. This non-metastatic neoplasm is rare in the general population but common in patients with familial cancer predisposition conditions known as familial adenomatous polyposis (FAP) or Gardner syndrome. Within fibromatosis/desmoid tumors, specific S45F mutations in CTNNB1 are associated with a worse 5-year recurrence-free survival compared to tumors with other or no CTNNB1 mutations. In addition, increased local recurrence has been associated with the S45F mutation in this neoplasm.

A single study has identified mutations in CTNNB1 (T41A, S45F and S45P) in the sporadic desmoid tumors of children, which was not associated with familial adenomatous polyposis.

PubMed ID's
18832571, 22372443
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.

Share with your Physican

Print information for your Physician.

Print information

Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
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
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
NCT02609984 Trial of CMB305 and Atezolizumab in Patients With Sarcoma Trial of CMB305 and Atezolizumab in Patients With Sarcoma 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