CTNNB1

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 multi-step process that allows the protein to move into the 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.

pilomatricoma - caused by mutations in the CTNNB1 gene

Mutations in the CTNNB1 gene are found in almost all pilomatricomas, a type of noncancerous (benign) skin tumor associated with hair follicles. These mutations 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 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 abnormally activates 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, known as pilomatrix carcinoma, also usually has somatic mutations in the CTNNB1 gene. It is unclear why some pilomatricomas are cancerous but most others are not.

other cancers - associated with the CTNNB1 gene

Somatic mutations in the CTNNB1 gene have been identified in several types of cancer. These include colorectal, liver, and ovarian cancers, as well as a type of brain tumor called a medulloblastoma. 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 promotes the unchecked growth and division 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. It is unclear why mutations in this gene are associated with several different types of cancerous and noncancerous tumors.

other tumors - associated with the CTNNB1 gene

Somatic mutations in the CTNNB1 gene have also been associated with a type of tumor called a desmoid tumor or desmoid fibromatosis. These rare tumors arise from connective tissue, which provides strength and flexibility to structures such as bones, ligaments, and muscles. Desmoid tumors grow quickly and tend to recur after being removed, although they only rarely become cancerous (malignant).

CTNNB1 gene mutations are found in about 85 percent of all non-inherited (sporadic) desmoid tumors. Research has shown that these gain-of-function mutations prevent the breakdown of beta-catenin when it is no longer needed, which allows the protein to accumulate within cells. The excess beta-catenin promotes the unchecked growth and division of cells, allowing the formation of desmoid tumors.