Bone and Soft Tissue Sarcoma, PIK3CA, G1049R (c.3145G>C)

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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 PIK3CA  - General Description
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PIK3CA is a gene that provides the code for making one piece of the phosphatidylinositol 3-kinase (PI3K) protein, which is an enzyme that is part of an important signaling pathway (PI3K/AKT) involved in controlling the growth, division, survival, nutrient utilization, movement and structure of cells. PIK3CA encodes the catalytic subunit of PI3K, which is the part of the protein that lets it function as an enzyme. PI3K function is tightly maintained in normal cells. The enzymatic activity is activated by specific signals from growth factor receptor tyrosine kinases (RTKs) or from activated RAS proteins. PI3K then generates molecules that attract another enzyme (particularly AKT) to the cell membrane, where it is activated. The activated AKT acts on other proteins that regulate various cell processes that promotes cell growth and survival.

Mutations in PIK3CA lead to enhanced activation of its signaling function, thereby driving the tumorigenic process. These activating mutations are commonly associated with breast and colon cancer, and more rarely with melanoma of the skin. Defects in this gene have also been associated with ovarian cancer, endometrial cancer, and liver cancer.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified PIK3CA mutations across a broad-spectrum of cancer types. The highest incidence of PIK3CA mutations have been found in endometrial cancer (25%), breast cancer (20%), colon cancer (25%) and cancers of the head and neck (10%). In the other major tumor types, PIK3CA mutations have been found in less than 10% of cases that have been tested.

Sources: Genetics Home Reference
The PIK3CA gene encodes the p110 alpha catalytic subunit of the phosphoinositol 3-kinase (PI3K) complex. PI3K receives upstream activation signals from growth factor receptor tyrosine kinases (e.g. EGFR family members), and in turn signals through AKT and mTOR in order to promote cell survival, cell growth and cellular proliferation. PIK3CA mutations lead to increased activation of PI3K/AKT/mTOR signaling. PI3K function is opposed by PTEN, a lipid phosphatase that is often inactivated by mutations or silenced by methylation in many cancers.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified PIK3CA mutations across a broad-spectrum of cancer types. The highest incidence of PIK3CA mutations have been found in endometrial cancer (25%), breast cancer (20%), colon cancer (25%) and cancers of the head and neck (10%). In the other major tumor types, PIK3CA mutations have been found in less than 10% of cases that have been tested.

Sources: Genetics Home Reference
Expand Collapse G1049R (c.3145G>C)  in PIK3CA
The PIK3CA G1049R mutation arises from a single nucleotide change (c.3145G>C) and results in an amino acid substitution of the glycine (G) at position 1049 by an arginine (R).
The PIK3CA G1049R mutation arises from a single nucleotide change (c.3145G>C) and results in an amino acid substitution of the glycine (G) at position 1049 by an arginine (R).

In myxoid liposarcomas, PIK3CA mutations are associated with a statistically significant reduction in overall survival.

Liposarcomas have recently been characterized to harbor PIK3CA activating mutations in approximately 18% of cases. A number of targeted agents that inhibit the PI3-kinase (PI3K) pathway are currently undergoing phase I and phase II clinical testing across a number of cancer types, and activating mutations in PIK3CA are entry criteria for some of these investigations. However, the effectiveness of these drugs in the treatment of PIK3CA-mutated liposarcoma patients has not yet been established.

In myxoid liposarcomas, PIK3CA mutations are associated with a statistically significant reduction in overall survival.

Liposarcomas have recently been characterized to harbor PIK3CA activating mutations in approximately 18% of cases. A number of targeted agents that inhibit the PI3-kinase (PI3K) pathway are currently undergoing phase I and phase II clinical testing across a number of cancer types, and activating mutations in PIK3CA are entry criteria for some of these investigations. However, the effectiveness of these drugs in the treatment of PIK3CA-mutated liposarcoma patients has not yet been established.

PubMed ID's
20601955

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing all 7 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
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
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.
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