CHEK2

The CHEK2 gene provides instructions for making a protein called checkpoint kinase 2 (CHK2). This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing too rapidly or in an uncontrolled way.

The CHK2 protein is activated when DNA becomes damaged or when DNA strands break. DNA can be damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, and breaks in DNA strands also occur naturally when chromosomes exchange genetic material.

In response to DNA damage, the CHK2 protein interacts with several other proteins, including tumor protein 53 (which is produced from the TP53 gene). These proteins halt cell division and determine whether a cell will repair the damage or self-destruct in a controlled manner (undergo apoptosis). This process keeps cells with mutated or damaged DNA from dividing, which helps prevent the development of tumors.

breast cancer - associated with the CHEK2 gene

Inherited mutations in the CHEK2 gene have been identified in some cases of breast cancer. For example, a specific change in this gene is associated with a moderately increased risk of breast cancer, particularly in European populations. This mutation is a deletion of a single DNA building block (nucleotide) at position 1100 in the CHEK2 gene (written as 1100delC). The 1100delC mutation leads to the production of an abnormally short, nonfunctional version of the CHK2 protein. Without this protein, cells are unable to regulate cell division properly. As a result, DNA damage accumulates and cells can divide without control or order. If cell division is not tightly controlled, cancerous tumors can develop.

Li-Fraumeni syndrome - associated with the CHEK2 gene

Although most cases of Li-Fraumeni syndrome are associated with mutations in the TP53 gene, CHEK2 mutations have been identified in several families with cancers characteristic of this condition. The 1100delC mutation was identified in one of these families. Researchers are uncertain whether CHEK2 mutations actually cause Li-Fraumeni syndrome or are merely associated with an increased risk of several types of cancer, including those cancers often seen in Li-Fraumeni syndrome.

other cancers - associated with the CHEK2 gene

Mutations in the CHEK2 gene have also been found in other hereditary and nonhereditary (sporadic) cancers affecting many of the body's organs and tissues. Although the full range of cancers associated with CHEK2 mutations has not been determined, studies have associated mutations in this gene with prostate, lung, colon, kidney, thyroid, and ovarian cancers. CHEK2 mutations have also been found in some brain tumors and in a type of bone cancer called osteosarcoma.