Skip to main content
An official website of the United States government

Chordoma Study

About the Study

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.

Although chordomas are slow-growing, local recurrence is common. This is especially true among skull-base chordoma patients and can largely be explained by incomplete tumor resection resulting from the close proximity of the tumor in relation to vital structures. Currently, there is no clear clinical guidance on patient stratification regarding treatment, such as post-surgery radiation therapy. Additionally, treatment options for chordoma patients, particularly those with advanced disease, are still limited. A better understanding of chordoma's molecular processes is critically needed to develop prognostic predictions tools and to discover novel druggable targets.


NCI investigators have been studying chordoma families (families with multiple relatives with chordoma) since 1996. Among their major findings was the identification of an alteration in the T gene on the long arm of chromosome 6, that caused chordoma to develop in members of four of these families. The way in which the T gene is altered in these families is unusual. The sequence of the DNA 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.

In collaboration with neurosurgeons in China, DCEG investigators conducted the first and largest whole-genomic sequencing analysis of skull-base chordoma and provided a detailed genomic landscape of skull-base chordoma. Their investigation revealed potential driver events, mutational signatures, and outcome-related genomic features.

DCEG Chordoma Research

The goals of the research are to:

  • Find the genes that cause chordoma to occur in multiple relatives in a chordoma family;
  • Describe the clinical findings in people with familial chordoma;
  • Determine whether families prone to chordoma are at increased risk of other types of cancer;
  • Develop better health care choices for families who have an increased risk for developing chordoma;
  • Determine whether the genes that are altered in members of chordoma families play a role in the development of chordoma in people without a family history of this cancer in the general population; and,
  • Identify molecular driver events in chordoma progression to improve patient stratification and develop molecular treatment.

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.