A chordoma is a rare type of cancerous tumor that can occur anywhere along the spine, from the base of the skull to the tailbone. Chordomas grow slowly, gradually extending into the bone and soft tissue around them. They often recur after treatment, and in about 40 percent of cases the cancer spreads (metastasizes) to other areas of the body, such as the lungs.

Approximately half of all chordomas occur at the base of the spine (sacrum), about one third occur in the base of the skull (occiput), and the rest occur in the cervical (neck), thoracic (upper back), or lumbar (lower back) vertebrae of the spine. As the chordoma grows, it puts pressure on the adjacent areas of the brain or spinal cord, leading to the signs and symptoms of the disorder. A chordoma anywhere along the spine may cause pain, weakness, or numbness in the back, arms, or legs. A chordoma at the base of the skull (occipital chordoma) may lead to double vision (diplopia) and headaches. A chordoma that occurs in the tailbone (coccygeal chordoma) may result in a lump large enough to be felt through the skin and may cause problems with bladder or bowel function.

Chordomas typically occur in adults between ages 40 and 70. About 5 percent of chordomas are diagnosed in children. For reasons that are unclear, males are affected about twice as often as females.

Chordomas are rare, occurring in approximately 1 per million individuals each year. Chordomas comprise fewer than 1 percent of tumors affecting the brain and spinal cord.

Changes in the TBXT gene have been associated with chordoma. An inherited duplication of the TBXT gene identified in a few families is associated with an increased risk of developing a chordoma. Duplications or increases in activity (expression) of the TBXT gene have also been identified in people with chordoma who have no history of the disorder in their family. In these individuals, the changes occur only in the tumor cells and are not inherited.

The TBXT gene provides instructions for making a protein called brachyury. Brachyury is a member of a protein family called T-box proteins, which play critical roles during embryonic development. T-box proteins regulate the activity of other genes by attaching (binding) to specific regions of DNA. On the basis of this action, T-box proteins are called transcription factors.

The brachyury protein is especially important for the early development of the spine. In human embryos, a structure called the notochord is the precursor of the spinal column. The notochord disappears before birth, but in a small percentage of individuals, some of its cells remain in the base of the skull or in the spine. In rare cases these cells begin to grow and divide uncontrollably, invading the nearby bone and soft tissue and resulting in the development of a chordoma.

Duplications and increases in expression of the TBXT gene both result in the production of excess brachyury protein. The specific mechanism by which excess brachyury protein contributes to the development of chordomas is unclear. Some people with chordoma do not have changes in the TBXT gene, and the cause of the disorder in these individuals is unknown.

Genetic Testing Information

• Genetic Testing Registry: Chordoma

Genetic and Rare Diseases Information Center

• Chordoma

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• CHORDOMA, SUSCEPTIBILITY TO; CHDM

Scientific Articles on PubMed

• PubMed

• Aguiar Junior S, Andrade WP, Baiocchi G, Guimaraes GC, Cunha IW, Estrada DA, Suzuki SH, Kowalski LP, Lopes A. Natural history and surgical treatment of chordoma: a retrospective cohort study. Sao Paulo Med J. 2014;132(5):297-302. doi: 10.1590/1516-3180.2014.1325628. Epub 2014 Jul 29. Citation on PubMed
• Casali PG, Stacchiotti S, Sangalli C, Olmi P, Gronchi A. Chordoma. Curr Opin Oncol. 2007 Jul;19(4):367-70. doi: 10.1097/CCO.0b013e3281214448. Citation on PubMed
• Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM, Baker LH. Chordoma: the nonsarcoma primary bone tumor. Oncologist. 2007 Nov;12(11):1344-50. doi: 10.1634/theoncologist.12-11-1344. Citation on PubMed
• Kelley MJ, Shi J, Ballew B, Hyland PL, Li WQ, Rotunno M, Alcorta DA, Liebsch NJ, Mitchell J, Bass S, Roberson D, Boland J, Cullen M, He J, Burdette L, Yeager M, Chanock SJ, Parry DM, Goldstein AM, Yang XR. Characterization of T gene sequence variants and germline duplications in familial and sporadic chordoma. Hum Genet. 2014 Oct;133(10):1289-97. doi: 10.1007/s00439-014-1463-z. Epub 2014 Jul 4. Citation on PubMed
• Presneau N, Shalaby A, Ye H, Pillay N, Halai D, Idowu B, Tirabosco R, Whitwell D, Jacques TS, Kindblom LG, Bruderlein S, Moller P, Leithner A, Liegl B, Amary FM, Athanasou NN, Hogendoorn PC, Mertens F, Szuhai K, Flanagan AM. Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study. J Pathol. 2011 Feb;223(3):327-35. doi: 10.1002/path.2816. Epub 2010 Nov 24. Citation on PubMed
• Sciubba DM, Chi JH, Rhines LD, Gokaslan ZL. Chordoma of the spinal column. Neurosurg Clin N Am. 2008 Jan;19(1):5-15. doi: 10.1016/j.nec.2007.09.006. Citation on PubMed
• Stacchiotti S, Sommer J; Chordoma Global Consensus Group. Building a global consensus approach to chordoma: a position paper from the medical and patient community. Lancet Oncol. 2015 Feb;16(2):e71-83. doi: 10.1016/S1470-2045(14)71190-8. Citation on PubMed
• Walcott BP, Nahed BV, Mohyeldin A, Coumans JV, Kahle KT, Ferreira MJ. Chordoma: current concepts, management, and future directions. Lancet Oncol. 2012 Feb;13(2):e69-76. doi: 10.1016/S1470-2045(11)70337-0. Citation on PubMed
• Yakkioui Y, van Overbeeke JJ, Santegoeds R, van Engeland M, Temel Y. Chordoma: the entity. Biochim Biophys Acta. 2014 Dec;1846(2):655-69. doi: 10.1016/j.bbcan.2014.07.012. Epub 2014 Sep 3. Citation on PubMed
• Yang XR, Ng D, Alcorta DA, Liebsch NJ, Sheridan E, Li S, Goldstein AM, Parry DM, Kelley MJ. T (brachyury) gene duplication confers major susceptibility to familial chordoma. Nat Genet. 2009 Nov;41(11):1176-8. doi: 10.1038/ng.454. Epub 2009 Oct 4. Citation on PubMed or Free article on PubMed Central