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New genetic findings emerge from chordoma Natural History Study

This paper represents the first notable findings to emerge from the chordoma cohort of the National Cancer Institute's Natural History Study of Rare Solid Tumors.


Photo: Dr. Mary Frances Wedekind at our 2023 International Chordoma Research Workshop

Researchers at the U.S. National Cancer Institute (NCI) have published new results from their chordoma Natural History Study. The paper sheds light on possible inherited genetic predispositions to chordoma.

The study was done by geneticist and genetic counselor Dr. Margarita Raygada, principal investigator Dr. Mary Frances Wedekind, and colleagues in the NCI’s MyPART Network. The team performed germline genetic testing on blood or saliva samples of 24 chordoma patients. Germline genetic testing is a type of test that looks for changes (mutations) in the DNA of non-cancer cells; these changes are present at birth and are sometimes inheritable (passed down from parent to offspring). The researchers discovered that 9 of the chordoma patients in this small study harbor mutations in genes known to predispose people to other cancers such as breast, colon, and prostate.

While there are no immediate implications of these findings for the treatment of chordoma, individuals who possess the reported mutations are at higher risk for developing certain other cancers. Because of this the authors recommend that germline genetic testing be considered for all chordoma patients so that patients who harbor these mutations and their first-degree relatives can receive appropriate preventative screening aimed at early detection of the other cancers associated with these mutations.

Interestingly, nearly all of the mutations found in this study were related to DNA damage repair pathways, critical systems in our cells that fix genetic material when it gets damaged. This is consistent with evidence from others such as Dr. Stefan Frohling’s team implicating defective DNA damage repair in chordoma formation, and reinforces findings from Chordoma Foundation Labs that a phenomenon called replication stress could play an important role in chordoma biology. Scientists in our lab are working intensively to find ways to target replication stress in chordoma with the goal of translating new treatment strategies into new clinical trials.

For additional information on potential implications of this study for chordoma patients, see the Q&A section below.

Continued enrollment is critical to improving chordoma treatment options

This paper represents the first notable findings to emerge from the chordoma cohort of the NCI’s Natural History Study of Rare Solid Tumors since its inception in 2021. In that time more than 120 chordoma patients have enrolled in the study — more than any other rare cancer being studied through this MyPART initiative. This is a testament to the remarkable level of participation from the chordoma community, and we’re thankful both to those who participated and to everyone who helped make our partnership with the NCI on this project possible.

We continue to encourage chordoma patients and survivors anywhere in the world and at any stage of treatment — before, during, or after — to enroll in the Natural History Study. Your participation will help researchers continue to uncover important aspects of chordoma’s biology and answer questions that will help accelerate and enable future clinical trials. Participation also benefits individual patients, who gain access to experts with extensive chordoma experience, as well as free genetic testing and genetic counseling.

Learn more here, and contact our Patient Navigators with questions about how to participate in the Natural History Study.

We’re grateful to the MyPART team for their work on this publication and their ongoing commitment to chordoma patients and families.

Q&A for chordoma patients about the new publication

  • How can I access germline genetic testing? You can enroll in the NCI’s Natural History Study; all new participants will receive this test and learn about the results from a genetic counselor for free. First degree relatives of patients who are found to have cancer predisposing germline mutations are also able to obtain free germline genetic testing through this study. Alternatively, you can seek the test from a cancer genetics clinic at an academic cancer center (be sure to ask for “germline genetic testing”). The testing is typically covered by insurance for U.S. chordoma patients. It’s performed using a saliva or blood sample; you will not be asked to provide a tumor sample.

  • If my germline genetic test reveals mutations in cancer genes, what does it mean for me? Your genetic counselor may recommend increased preventative screening for other cancers. They will meet with you before and after you undergo this testing to help explain its implications.

  • What do these results mean for close relatives? Germline genetic testing reveals mutations that are inheritable. If your test shows that you harbor certain mutations, your genetic counselor may or may not recommend that your close relatives be tested for them too.

  • Can the results of my germline genetic test help my doctor choose a drug to treat my chordoma, or tell me anything about my prognosis? Germline genetic testing is performed on non-cancer cells to look for genetic changes in all the cells in your body; it’s different from genetic testing performed on tumors, which looks for mutations that arise within cancer cells. While the latter test can sometimes guide treatment decisions and help determine prognosis in some cancer types, at present it is unlikely that information gleaned from germline testing would inform chordoma treatment strategy or prognosis.

  • Could the mutations identified in this study be causing chordoma? This is not yet known.

  • Does this study mean that chordoma is hereditary? This study suggests that relatively common germline mutations that can be hereditary may be associated with chordoma. However, inherited chordoma has only been found in a very small number of families (less than 20) in the world. You can read more about that here.

If you have additional questions about what this study might mean for you, contact our Patient Navigators.

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