uestion 1: What is chordoma and how does the TBXT gene increase the risk of developing it?

Chordoma is a rare type of cancerous tumor that develops along the spine or at the base of the skull. It originates from remnants of the notochord, a structure present during embryonic development that normally disappears. Changes in the TBXT gene, particularly duplications or increased activity (expression), lead to the production of excess brachyury protein. This excess protein is associated with an increased risk of chordoma, though the exact mechanism by which it drives tumor development is still being researched.

TBXT gene

The TBXT gene provides instructions for making the brachyury protein, which is essential for embryonic development and the formation of the notochord.

Normal Function

The TBXT gene provides instructions for making a protein called brachyury. Brachyury is a member of a protein family called T-box proteins, which play critical roles during embryonic development. T-box proteins regulate the activity of other genes by attaching (binding) to specific regions of DNA. On the basis of this action, T-box proteins are called transcription factors.

The brachyury protein is important for the development of the notochord, which is the precursor of the spinal column in the embryo. The notochord helps control the development of the neural tube, which is a layer of cells that ultimately develops into the brain and spinal cord.

Health Conditions Related to Genetic Changes

Chordoma

Changes in the TBXT gene have been associated with chordoma. A chordoma is a cancerous tumor that occurs along the spine or in the base of the skull. The tumor develops from residual cells of the notochord that begin to grow and divide uncontrollably.

An inherited duplication of the TBXT gene is associated with an increased risk of developing a chordoma.
Duplications or increases in activity (expression) of the TBXT gene have also been identified in people with chordoma who have no history of the disorder in their family; in these cases, the changes occur only in the tumor cells and are not inherited.
These genetic changes result in the production of excess brachyury protein, though the specific mechanism contributing to tumor development is unclear.

Other disorders

A variation of the TBXT gene is associated with an increased risk of neural tube defects, including spina bifida. Neural tube defects result when the neural tube fails to close completely during the first few weeks of embryonic development.

The TBXT gene variation, known as TIVS7 T/C, changes a single DNA building block (nucleotide) in a region of the gene known as intron 7. Researchers suggest this may affect the regulation of brachyury protein production in early development.

Other Names for This Gene

BRAC_HUMAN
brachyury protein
protein T
T
T brachyury homolog
T brachyury transcription factor
T, brachyury homolog (mouse)
TFT