A desmoid tumor is an abnormal growth that arises from connective tissue, which is the tissue that provides strength and flexibility to structures such as bones, ligaments, and muscles. Typically, a single tumor develops, although some people have multiple tumors. The tumors can occur anywhere in the body. Tumors that form in the abdominal wall are called abdominal desmoid tumors; those that arise from the tissue that connects the abdominal organs are called intra-abdominal desmoid tumors; and tumors found in other regions of the body are called extra-abdominal desmoid tumors. Extra-abdominal tumors occur most often in the shoulders, upper arms, and upper legs.

Desmoid tumors are fibrous, much like scar tissue. They are generally not considered cancerous (malignant) because they do not spread to other parts of the body (metastasize); however, they can aggressively invade the surrounding tissue and can be very difficult to remove surgically. These tumors often recur, even after apparently complete removal.

The most common symptom of desmoid tumors is pain. Other signs and symptoms, which are often caused by growth of the tumor into surrounding tissue, vary based on the size and location of the tumor. Intra-abdominal desmoid tumors can block the bowel, causing constipation. Extra-abdominal desmoid tumors can restrict the movement of affected joints and cause limping or difficulty moving the arms or legs.

Desmoid tumors occur frequently in people with an inherited form of colon cancer called familial adenomatous polyposis (FAP). These individuals typically develop intra-abdominal desmoid tumors in addition to abnormal growths (called polyps) and cancerous tumors in the colon. Desmoid tumors that are not part of an inherited condition are described as sporadic.

Mutations in the CTNNB1 gene or the APC gene cause desmoid tumors. CTNNB1 gene mutations account for around 85 percent of sporadic desmoid tumors. APC gene mutations cause desmoid tumors associated with familial adenomatous polyposis as well as 10 to 15 percent of sporadic desmoid tumors. Both genes are involved in an important cell signaling pathway that controls the growth and division (proliferation) of cells and the process by which cells mature to carry out specific functions (differentiation).

The CTNNB1 gene provides instructions for making a protein called beta-catenin. As part of the cell-signaling pathway, beta-catenin interacts with other proteins to control the activity (expression) of particular genes, which helps promote cell proliferation and differentiation. CTNNB1 gene mutations lead to an abnormally stable beta-catenin protein that is not broken down when it is no longer needed. The protein accumulates in cells, where it continues to function in an uncontrolled way.

The protein produced from the APC gene helps regulate levels of beta-catenin in the cell. When beta-catenin is no longer needed, the APC protein attaches (binds) to it, which signals for it to be broken down. Mutations in the APC gene that cause desmoid tumors lead to a short APC protein that is unable to interact with beta-catenin. As a result, beta-catenin is not broken down and, instead, accumulates in cells. Excess beta-catenin, whether caused by CTNNB1 or APC gene mutations, promotes uncontrolled growth and division of cells, allowing the formation of desmoid tumors.

Normal Function

The CTNNB1 gene provides instructions for making a protein called beta-catenin. This protein is present in many types of cells and tissues, where it is primarily found at junctions that connect neighboring cells (adherens junctions). Beta-catenin plays an important role in sticking cells together (cell adhesion) and in communication between cells.

The beta-catenin protein is also involved in cell signaling as an essential part of the Wnt signaling pathway. Certain proteins in this pathway attach (bind) to beta-catenin, which triggers a multistep process that allows the protein to move into the cell nucleus. Once in the nucleus, beta-catenin interacts with other proteins to control the activity (expression) of particular genes. The Wnt signaling pathway promotes the growth and division (proliferation) of cells and helps determine the specialized functions a cell will have (differentiation). Wnt signaling is known to be involved in many aspects of development before birth. In adult tissues, this pathway plays a role in the maintenance and renewal of stem cells, which are cells that help repair tissue damage and can give rise to other types of cells.

Among its many activities, beta-catenin appears to play an important role in the normal function of hair follicles, which are specialized structures in the skin where hair growth occurs. This protein is active in cells that make up a part of the hair follicle known as the matrix. These cells divide and mature to form the different components of the hair follicle and the hair shaft. As matrix cells divide, the hair shaft is pushed upward and extends beyond the skin.

Health Conditions Related to Genetic Changes

Desmoid tumor

Mutations in the CTNNB1 gene can cause a type of aggressive but noncancerous (benign) growth called a desmoid tumor. CTNNB1 gene mutations are found in about 85 percent of all noninherited (sporadic) desmoid tumors. These rare tumors arise from connective tissue, which provides strength and flexibility to structures such as bones, ligaments, and muscles. The tumors are often found in the abdomen, shoulders, upper arms, or upper legs. The CTNNB1 gene mutations that cause desmoid tumors are somatic, which means they are acquired during a person's lifetime and are present only in tumor cells. Somatic mutations are not inherited.

The CTNNB1 gene mutations that cause desmoid tumors usually occur in a region of the gene called exon 3. They change single protein building blocks (amino acids) in the beta-catenin protein. These mutations lead to an abnormally stable beta-catenin protein that is not broken down when it is no longer needed. As a result, the protein accumulates within cells. Excess beta-catenin promotes the uncontrolled proliferation of cells, allowing the formation of desmoid tumors.

Pilomatricoma

Somatic mutations in the CTNNB1 gene are found in almost all pilomatricomas, a type of benign skin tumor associated with hair follicles.

The CTNNB1 gene mutations found in pilomatricomas are described as gain-of-function mutations. They cause the beta-catenin protein to be turned on all the time (constitutively active), which leads to the abnormal activation of certain genes. These genes increase the proliferation and differentiation of cells associated with the hair follicle matrix. The cells divide too quickly and in an uncontrolled way, leading to the formation of a pilomatricoma.

Almost all pilomatricomas are benign, but a very small percentage are cancerous (malignant). The malignant version of this tumor is known as a pilomatrix carcinoma. Like pilomatricomas, pilomatrix carcinomas have somatic mutations in the CTNNB1 gene. It is unclear why some of these tumors are cancerous but most others are not.

Wilms tumor

Mutations in the CTNNB1 gene have been found in Wilms tumor, a rare form of kidney cancer that occurs almost exclusively in children. These mutations are somatic and occur only in kidney cells that give rise to the tumor. CTNNB1 gene mutations in Wilms tumor result in an overly active protein. This active beta-catenin protein promotes Wnt signaling longer than normal, which leads to the unchecked proliferation of kidney cells and tumor development.

Aldosterone-producing adenoma

MedlinePlus Genetics provides information about Aldosterone-producing adenoma

Ovarian cancer

MedlinePlus Genetics provides information about Ovarian cancer

Other cancers

Somatic mutations in the CTNNB1 gene have been identified in several other types of cancer. These include colorectal, liver, thyroid, ovarian, endometrial, and skin cancers, as well as a type of brain tumor called a medulloblastoma, among others. Studies suggest that gain-of-function mutations in the CTNNB1 gene prevent the breakdown of beta-catenin when it is no longer needed, which allows the protein to accumulate within cells. The excess beta-catenin moves into the cell nucleus and promotes the unchecked proliferation of cells, allowing cancerous tumors to develop.

Because mutations in the CTNNB1 gene can cause normal cells to become cancerous, CTNNB1 belongs to a class of genes known as oncogenes. Sometimes, mutations in other oncogenes occur together with CTNNB1 gene mutations to cause cancer. It is not well understood why mutations in the CTNNB1 gene are associated with several different types of cancerous and noncancerous tumors.

Other Names for This Gene

• armadillo
• beta-catenin
• catenin (cadherin-associated protein), beta 1
• catenin (cadherin-associated protein), beta 1, 88kDa
• catenin beta-1
• CTNB1_HUMAN
• CTNNB

Genomic Location

Normal Function

The APC gene provides instructions for making the APC protein, which plays a critical role in several cellular processes. The APC protein acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. It helps control how often a cell divides, how it attaches to other cells within a tissue, and whether a cell moves within or away from a tissue. This protein also helps ensure that the number of chromosomes in a cell is correct following cell division. The APC protein accomplishes these tasks mainly through association with other proteins, especially those that are involved in cell attachment and signaling.

One protein with which APC associates is beta-catenin. Beta-catenin helps control the activity (expression) of particular genes and promotes the growth and division (proliferation) of cells and the process by which cells mature to carry out specific functions (differentiation). Beta-catenin also helps cells attach to one another and is important for tissue formation. Association of APC with beta-catenin signals for beta-catenin to be broken down when it is no longer needed.

Health Conditions Related to Genetic Changes

Desmoid tumor

Several mutations in the APC gene have been found in people with a type of aggressive but noncancerous (benign) growth called a desmoid tumor. These rare tumors arise from connective tissue, which provides strength and flexibility to structures such as bones, ligaments, and muscles. APC gene mutations typically cause formation of desmoid tumors in the abdomen, but these tumors can also occur in other parts of the body. Although APC-related desmoid tumors are commonly associated with a form of colon cancer called familial adenomatous polyposis (described below), APC gene mutations can cause tumors in individuals without this inherited disease. APC gene mutations are found in about 10 to 15 percent of non-inherited (sporadic) desmoid tumors; these mutations are somatic, which means they are acquired during a person's lifetime and are present only in tumor cells.

Most APC gene mutations that cause sporadic desmoid tumors lead to an abnormally short APC protein. The shortened protein is unable to interact with the beta-catenin protein, which prevents the breakdown of beta-catenin when it is no longer needed. Excess beta-catenin promotes uncontrolled growth and division of cells, allowing the formation of desmoid tumors.

Familial adenomatous polyposis

More than 700 mutations in the APC gene have been identified in families with the classic and attenuated types of familial adenomatous polyposis (FAP). Most of these mutations lead to the production of an abnormally short, nonfunctional version of the APC protein. This short protein cannot suppress the cellular overgrowth that leads to the formation of abnormal growths (polyps) in the colon, which can become cancerous. The most common mutation in FAP is a deletion of five building blocks of DNA (nucleotides) in the APC gene. This mutation changes the sequence of the building blocks of proteins (amino acids) in the resulting APC protein.

Although most people with FAP will develop colorectal cancer, the number of polyps and the time frame in which they become cancerous depend on the location of the mutation in the APC gene. The location of the mutation also determines whether an individual with FAP is predisposed to developing desmoid tumors (described above).

Primary macronodular adrenal hyperplasia

MedlinePlus Genetics provides information about Primary macronodular adrenal hyperplasia

Other cancers

Mutations in the APC gene are also responsible for a disorder called Turcot syndrome, which is closely related to familial adenomatous polyposis. Turcot syndrome is an association of colorectal cancer with a type of cancerous brain tumor called a medulloblastoma. Approximately two-thirds of people with Turcot syndrome have mutations in the APC gene.

A certain mutation in the APC gene (unrelated to Turcot syndrome) is found in approximately 6 percent of people with Ashkenazi (eastern and central European) Jewish heritage. This mutation replaces the amino acid isoleucine with the amino acid lysine at position 1307 in the APC protein (written as Ile1307Lys or I1307K). This change was initially thought to be harmless, but has been shown to be associated with a 10 percent to 20 percent increased risk of colon cancer.

Somatic mutations in the APC gene may be involved in the development of a small percentage of stomach (gastric) cancers.

Other Names for This Gene

• adenomatous polyposis coli
• APC_HUMAN
• DP2
• DP2.5
• DP3
• FAP
• FPC
• GS
• PPP1R46
• WNT signaling pathway regulator

Genomic Location

Most desmoid tumors are sporadic and are not inherited. Sporadic tumors result from gene mutations that occur during a person's lifetime, called somatic mutations. A somatic mutation in one copy of the gene is sufficient to cause the disorder. Somatic mutations in either the CTNNB1 or the APC gene can cause sporadic desmoid tumors.

An inherited mutation in one copy of the APC gene causes familial adenomatous polyposis and predisposes affected individuals to develop desmoid tumors. The desmoid tumors occur when a somatic mutation occurs in the second copy of the APC gene. In these cases, the condition is sometimes called hereditary desmoid disease.

Some people with desmoid tumors have symptoms, while others do not. Symptoms can include pain, swelling in the area of the tumor, sleep loss, or difficulty moving. For people without symptoms, these tumors can be discovered if the person has an imaging test for another reason.

Imaging: If you have symptoms of a desmoid tumor, your doctor may use imaging scans such as CT, MRI, or ultrasound to see where the tumor is and its size.

Biopsy: To check if the tumor is a desmoid tumor your doctor will do a biopsy, taking a small amount of the tumor out with a needle. A pathologist will study the cells under the microscope to see what kind of tumor it is. Depending on the tumor's location, it may be difficult for the doctor to take a biopsy.

Treatment for each patient will be unique so you should go to an expert in sarcoma treatment to decide the best approach for your tumor.

Desmoid tumors can be hard to predict. They can shrink and go away on their own, they can remain the same size, or they can grow quickly.

Treatment options to discuss with your doctor include:

Watch and wait: In some cases, the tumor grows very slowly, or even shrinks without any treatment. It may be safest for your doctor to check your tumor regularly without treating it.

Surgery: Surgery has been a standard treatment for desmoid tumors in the past but this may be changing. Given that the tumor often returns to the same location after surgery, doctors are looking for other treatment options.

Radiation therapy: Radiation therapy is a treatment option for some desmoid tumors. Given that radiation therapy can cause other cancers in the future, it is important to discuss alternatives with your doctor.

Chemotherapy: There is no standard chemotherapy for desmoid tumors but promising new drugs have been shown to shrink these tumors.

It is important to discuss these different options with your doctor and seek second opinions, if possible.

The estimate of how a disease will affect you long-term is called prognosis. Every person is different and prognosis will depend on many factors, such as:

• Where the tumor is in your body
• How fast the tumor grows
• How much of the tumor was taken out during surgery

If you want information on your prognosis, it is important to talk to your doctor. NCI also has resources to help you understand cancer prognosis.

Doctors estimate desmoid tumor survival rates by how groups of people with desmoid tumors have done in the past. Given that there are so few desmoid tumor patients, survival rates may not be very accurate. They also don’t consider newer treatments being developed.

Most desmoid tumors do not impact lifespan but they are very difficult to get rid of and can be painful to live with. Desmoid tumors growing in the abdomen can cause problems, such as blocking your intestines. It is important that your doctor monitor the growth of these tumors carefully.

Desmoid tumors are rare, affecting an estimated 1 to 2 per 500,000 people worldwide. In the United States, 900 to 1,500 new cases are diagnosed per year. Sporadic desmoid tumors are more common than those associated with familial adenomatous polyposis.