Chordoma (chordoma) - Gen T

Chordoma is a rare type of malignancy that can occur anywhere along the spine from the skull base to the coccyx. Chordomas grow slowly, gradually spreading in the bone and soft tissue around them. Often, such tumor recurs after treatment, and approximately 40% of cases the cancer spreads to other areas of the body such as the lungs.

Approximately half of all chordoma occurs in the sacrum, about one third is produced in the occiput, and the rest are produced in the neck and upper or lower back. As chordoma grows, it exerts pressure on adjacent areas of the brain or spinal cord, leading to the signs and symptoms of the disease. A chordoma anywhere along the spine can cause pain, weakness, or numbness in the back, arms or legs. Chordoma in the skull base (occipital chordoma) can cause diplopia and headache. Chordoma produced in the coccyx (chordoma coccygeal) can result in a sufficient mass to be palpated through the skin and can lead to problems with bladder function or bowel. Chordomas usually occur in adults between 40 and 70 years old. About 5% of chordoma are diagnosed in children. For reasons that are unclear, males are affected about twice as much as women.

This process is due to genetic alterations in the gene of T (T brachyury transcription factor), located on the long arm of chromosome 6 (6q27), encoding the protein synthesis brachyury. The brachyury belongs to a family of proteins called T-box proteins, which play a critical role during embryonic development. T-box proteins regulate the activity of other genes by binding to specific DNA regions, so are considered transcription factors. The brachyury protein is important for the development of the notochord, the precursor of the spinal column in the embryo. The notochord disappears before birth, but in a small percentage of individuals, some cells remain at the base of the skull or spine. Notochord helps control the development of neural tube that eventually becomes the brain and spinal cord.

In affected individuals, chordoma develops from residual cells of the notochord, which begin to grow and divide uncontrollably. T inherited gene duplication identified in a few families, is associated with an increased risk of developing chordoma. Duplications or increases in the expression of the T gene have also been identified in people with chordoma who have no history of the disease in his family. In these individuals, the changes only occur in tumor cells and not inherited. Duplications and increases in expression of T gene result in excess encoding brachyury protein. However, the specific mechanism by which excess protein brachyury contributes to the development of chordoma is unclear. In some people with chordoma they have not identified changes in the T gene, so the cause of the disease is unknown in these individuals.

When developing a chordoma is associated with a doubling of T gene inherited from one parent, one copy of the altered gene in each cell it is sufficient to increase the risk of disease, implying an autosomal dominant inheritance. People with this duplication inherit an increased risk of developing the disease, not the disease itself. Other cases of chordoma are sporadic, meaning that occur in people with no history of disease in your family.

Tests in IVAMI: in IVAMI perform detection of mutations associated with chordoma, by complete PCR amplification of the exons of the T gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).