Chordoma is a rare bone cancer that is diagnosed in only about 300 patients in the U.S. each year. It develops at the base of the skull, in a vertebra, or at end of the spine (in the sacrum or the coccyx [the tail bone]) with about equal frequency. The cells that give rise to chordoma come from the notochord. The notochord is an important structure in the early embryo that disappears before birth. However, even after birth, some cells from the notochord remain in bones at the base of the skull, in vertebrae, and in the tail bone. Rarely, one of these cells, which are called notochord remnants, undergoes changes that give rise to a chordoma.
Chordoma is diagnosed most often in people who are in their late 50s, but it can occur much earlier or later. It develops in males more often than females and, for unknown reasons, is rare in African Americans. There are few effective treatments and no cure for chordoma. Most people with chordoma die within 10 years of diagnosis.
No specific environmental factors that increase the risk of developing chordoma have been identified. And, the vast majority of people with chordoma have no other family members with this cancer. However, a small number of families with multiple relatives with chordoma have been reported worldwide. In most of them, chordoma has occurred in a parent and one or more of his/her children. This pattern suggests that in these families, chordoma results from the presence of an altered or mutated gene that has been passed from the affected parent to some of his/her children.
NCI investigators have been studying chordoma families (families with multiple relatives with chordoma) since 1996. Recently, they identified the altered gene that caused chordoma to develop in members of four of these families. The altered gene is the T gene on the long arm of chromosome 6. The way in which the T gene is altered in these families is unusual. The sequence of the DNA within this gene has not been changed or mutated; instead the entire T gene has been duplicated.
The T gene makes a protein called brachyury that plays an important role in the development of the notochord. Brachyury is present in notochord cells and also in chordomas, but it is not found in most other types of cancer or in the normal cells around a chordoma. At the present time, no one knows why an extra copy of the T gene in members of these four families increases their risk of developing chordoma.
Some of the chordoma families studied by investigators did not have an extra copy of the T gene. This suggests that mutations of other gene(s) or an as yet unidentified process involving the T gene caused the increased risk for chordoma in these families.
The goals of the research are to:
DCEG investigators are seeking chordoma families to participate in research to identify additional genes that increase the risk of family members developing chordoma. To learn more, please see our research on Familial Chordoma.
DCEG investigators are also seeking individuals with chordoma who are the only member of their family with this cancer. These types of individuals may participate in research to determine whether “familial chordoma” genes play a role in causing people without a family history of chordoma to develop this cancer. To learn more, please see our research on Non-Familial Chordoma.
For more information, contact Xiaohong Rose Yang.