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.
Background
Investigators in the Genetic Epidemiology Branch (GEB), National Cancer Institute (NCI), 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 GEB 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.
Purposes of GEB’s 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; and,
- 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.
GEB 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 about our research on Familial Chordoma, click here.
GEB 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 about our research on Non-Familial Chordoma, click here.
Familial Chordoma Study
What Does Participation in the Familial Chordoma Study Involve?
Those who choose to participate in the Familial Chordoma Study will be asked to:
- Provide a blood sample or saliva as a source of DNA for genetic studies on chordoma or related cancers
- Provide personal medical and family history information; and,
- Give us permission to obtain past medical records about chordoma, other cancers and related illnesses, and a small piece of chordoma or any other cancer that was stored after surgery.
Blood for the research can be drawn by a participant’s own physician or at a local laboratory and mailed to us. The other activities can be carried out in a participant’s home.
In addition, individuals from some chordoma families may be invited to the Clinical Center of the National Institutes of Health (NIH), in Bethesda, MD, to participate in clinical studies. These studies include having a physical examination and donating blood for research; they may also include undergoing magnetic resonance (MR) imaging studies of the base of the skull and entire spine. Results of the clinical studies will be discussed with the participants before they return home and given to them to share with their primary doctors.
Participants and family members will be able to ask questions and stay in touch with the research team. Participants will be asked to complete a yearly follow-up form to update medical information. We will provide participants with the overall findings of the study when analysis of information from the study is completed.
This study has been reviewed and approved by the Institutional Review Board (IRB) of the NCI. NCI is required by Federal law not to reveal any personal information that is collected from study participants to anyone other than persons directly involved with the study. A system is in place to ensure your privacy; in addition, all information obtained as part of this research is protected from disclosure by a Certificate of Confidentiality issued by the NCI.
Costs. NCI will pay for all clinical studies done at the NIH Clinical Center and for travel to and from Bethesda, MD, for participants.
Treatment. Treatment is not offered as part of this study. However, if the need arises, we will discuss treatment options with participants. We will also provide assistance in establishing care with appropriate physicians as needed. Study participants will remain under the care of their primary doctors while participating in the study.
Who is Eligible to Participate in the Familial Chordoma Study?
To participate in the Familial Chordoma study, a family must have the following:
- Two or more blood relatives with a history of chordoma
Family members who are eligible to participate include those with chordoma, and their parents, siblings and children. We may also invite other blood relatives to join the study if they are genetically linked to family members with chordoma.
In addition, if children who have a parent with chordoma participate, we may invite their unaffected parent to join the study.
If your family has two or more blood relatives who have been diagnosed with chordoma and you and other family members are interested in contributing to research on familial chordoma, please complete and submit the Familial Chordoma study form . A research nurse will get back to you in a few days.
This information is not on a secure server, so if you prefer, you can call toll-free 1-800-518-8474 and ask to speak with Ms. Stephanie Steinbart about the Familial Chordoma Study. She is a research nurse who can answer your questions and provide additional information about this study.
Non-Familial Chordoma Study
What Does Participation in the Non-Familial Chordoma Study Involve?
Those who choose to participate in the Non-Familial Chordoma Study will be asked to:
- Provide a saliva sample as a source of DNA for genetic studies on chordoma or
related cancers;
- Provide personal medical and family history information by completing a self-administered questionnaire; and
- Give us permission to obtain past medical records about chordoma, and a small piece of chordoma that was stored after surgery.
People will be able to participate in this study from their homes. After they have contacted us to ask about this study, if they are interested in learning more about it, we will send them a letter that describes the study in more detail. We will then telephone them to determine whether they wish to participate in the research. If they decide to participate, we will mail a package to their home that contains all of the materials needed for the study. The package includes the study consent form, the personal and family medical history questionnaire, and the kit that contains a special plastic cup and a lid for using to collect a saliva sample. After they have signed the consent form, completed the questionnaire and collected the saliva sample, they can mail these back to us in a pre-addressed postage-paid envelope included in the package.
We will provide participants with the overall findings of the study when analysis of information from the study is completed.
Based on information we learn about a participant’s personal or family medical history or from the laboratory tests done on DNA from the saliva or chordoma samples, we may re-contact a participant and invite him/her, and possibly some close relatives, to participate in a separate clinical study related to the development of chordoma. If we re-contact people about the clinical study, they can decide at that time whether they want to participate in it.
This study has been reviewed and approved by the Special Studies Institutional Review Board (SSIRB) of the NCI. NCI is required by Federal law not to reveal any personal information that is collected from study participants to anyone other than persons directly involved with the study. A system is in place to ensure the privacy of all participants; in addition, all information obtained as part of this research is protected from disclosure by a Certificate of Confidentiality issued by the NCI.
Who is Eligible to Participate in the Non-Familial Chordoma Study?
To participate in the Non-Familial Chordoma study, a person must be:
- the only individual in his/her extended family diagnosed with chordoma, and
- at least 6 years old.
If the individuals with chordoma are between the ages of 6 and 17 years of age, a parent can serve as a proxy for them and complete the personal and family medical history questionnaire. A parent may also help them collect the saliva sample.
If only one person in your family has ever been diagnosed with chordoma and you are interested in contributing to research on non-familial chordoma, please complete and submit the Non-Familial Chordoma study form . A research nurse will get back to you in a few days.
This information is not on a secure server, so if you prefer, you can call toll-free 1-800-518-8474 and ask to speak with Ms. Stephanie Steinbart about the Non-Familial Chordoma Study. She is a research nurse who can answer your questions and provide additional information about this study.
Who are the Responsible Investigators?
One of the special features of the research conducted by investigators in the Genetic Epidemiology Branch is that it is carried out by a dedicated study team. Each member of the team brings special expertise to the study.
The Study Team for GEB’s chordoma research consists of the following individuals:
Alisa M. Goldstein, Ph.D. is a board certified Ph.D. medical geneticist. She has been involved in research to identify genes and environmental factors that increase a person's risk for develping cancer for over 20 years. She is the Principal Investigator of the Non-Familial Chordoma Study and serves as the senior consultant on laboratory and analytic aspects of both the Familial Chordoma Study and the Non-Familial Chordoma Study.
Dilys M. Parry, Ph.D. is a board certified Ph.D. medical geneticist. She has been involved in research on familial and hereditary cancers for 30 years. She began studying chordoma families in 1996 and then initiated the Familial Chordoma study. She is responsible for obtaining and analyzing the clinical information from both the Familial Chordoma Study and the Non-Familial Chordoma Study.
Deborah Zametkin, R.N., M.S.N. is a senior research nurse who has been working with patients with familial and hereditary cancers for 18 years. She has been involved in the Familial Chordoma Study since 1996 and now serves as the study manager for the Non-Familial Chordoma Study.
Rose Yang, Ph.D. is a tenure-track investigator who is interested in identifying genes and environmental factors that increase a person’s risk for developing cancer. She is responsible for deciding which laboratory studies should be done on DNA from members of chordoma families and from individuals who are the only person in their family with chordoma. She serves as the liaison between any laboratories involved in the chordoma research and the study team. She is also responsible for analyzing the laboratory data from the chordoma studies.
The study team collaborates with investigators from other institutions who are also studying chordoma or who have expertise in the diagnosis and treatment of chordoma or in state-of-the-art laboratory methods that can be used to examine biological specimens from members of chordoma families or from individuals who are the only person in their family with chordoma.
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