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Dilys M. Parry, Mary L. McMaster, Norbert J. Liebsch, Nicholas J. Patronas, Martha M. Quezado, Deborah Zametkin, Xiaohong R. Yang and Alisa M. Goldstein

. 1964 ; 26 : 88 – 90 . 5 Foote RF , Ablin G , Hall WW . Chordoma in siblings . Calif Med . 1958 ; 88 ( 5 ): 383 – 386 . 6 Kelley MJ , Shi J , Ballew B , Characterization of T gene sequence variants and germline duplications in familial and sporadic chordoma . Hum Genet . 2014 ; 133 ( 10 ): 1289 – 1297 . 7 Wang KE , Wu Z , Tian K , Familial chordoma: a case report and review of the literature . Oncol Lett . 2015 ; 10 ( 5 ): 2937 – 2940 . 8 Yang XR , Ng D , Alcorta DA , T (brachyury) gene duplication confers major

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Wesley Hsu, Ahmed Mohyeldin, Sagar R. Shah, Colette M. ap Rhys, Lakesha F. Johnson, Neda I. Sedora-Roman, Thomas A. Kosztowski, Ola A. Awad, Edward F. McCarthy, David M. Loeb, Jean-Paul Wolinsky, Ziya L. Gokaslan and Alfredo Quiñones-Hinojosa

gastrulation events and notochord development. 24 A study of 8 families with heritable chordoma found that duplications of the T (Brachyury) gene confer a major susceptibility to this malignancy. 34 Furthermore, Brachyury is expressed in embryonic notochord, 29 is essential for notochordal development, 7 and has been shown to be critical for morphogenetic migration of mesodermal cells during gastrulation. 8 , 19 , 30 Screening of Brachyury expression in chordoma revealed positive expression in 90% of all pathologically confirmed chordomas screened. 15 More recently

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Deric M. Park

, Rosenberg AE , Ramesh V : Aberrant hyperactivation of akt and Mammalian target of rapamycin complex 1 signaling in sporadic chordomas . Clin Cancer Res 15 : 1940 – 1946 , 2009 4 Presneau N , Shalaby A , Ye H , Pillay N , Halai D , Idowu B , : Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study . J Pathol 223 : 327 – 335 , 2011 5 Salisbury JR : [Embryology and pathology of the human notochord.] . Ann Pathol 21 : 479 – 488 , 2001 . (Fr) 6 Siu IM

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Hua Zhong, Zhihong Zhou, Guo-Hua Lv, Jing Li and Ming-Xiang Zou

Disclosures The authors report no conflict of interest. References 1 Bettegowda C , Yip S , Lo SL , Fisher CG , Boriani S , Rhines LD , : Spinal column chordoma: prognostic significance of clinical variables and T (brachyury) gene SNP rs2305089 for local recurrence and overall survival . Neuro Oncol 19 : 405 – 413 , 2017 2 Feng Y , Zhang Q , Wang Z , Yan B , Wei W , Li P : Overexpression of the BMP4/SMAD signaling pathway in skull base chordomas is associated with poor prognosis . Int J Clin Exp Pathol 8 : 8268 – 8275 , 2015

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Joseph L. Koen, Roger E. McLendon and Timothy M. George

embryonic cells and may be involved in regulation of axis formation. Development 107: 275–280, 1989 56. Morita Y : Neurenteric cyst or teratomatous cyst. J Neurosurg 80 : 179 , 1994 (Letter) Morita Y: Neurenteric cyst or teratomatous cyst. J Neurosurg 80: 179, 1994 (Letter) 57. Morrison K , Papapetrou C , Attwood J , et al : Genetic mapping of the human homologue (T) of mouse T (Brachyury) and a search for allele association between human T and spina bifida. Hum Mol Genet 5 : 669 – 674

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Ryohei Otani, Akitake Mukasa, Masahiro Shin, Mayu Omata, Shunsaku Takayanagi, Shota Tanaka, Keisuke Ueki and Nobuhito Saito

, Gikas P , Cannon SR , Gout I , : Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway . Br J Cancer 100 : 1406 – 1414 , 2009 24 Presneau N , Shalaby A , Ye H , Pillay N , Halai D , Idowu B , : Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study . J Pathol 223 : 327 – 335 , 2011 25 Roselli M , Fernando RI , Guadagni F , Spila A , Alessandroni J , Palmirotta R , : Brachyury, a driver of the epithelial

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John Henry Owen, Christine M. Komarck, Anthony C. Wang, Waleed M. Abuzeid, Richard F. Keep, Erin L. McKean, Stephen Sullivan, Xing Fan and Mark E. P. Prince

65 : 1514 – 1521 , 2006 16757128 10.1016/j.ijrobp.2006.02.059 32 Presneau N , Shalaby A , Ye H , Pillay N , Halai D , Idowu B , : Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study . J Pathol 223 : 327 – 335 , 2011 10.1002/path.2816 33 Rinner B , Froehlich EV , Buerger K , Knausz H , Lohberger B , Scheipl S , : Establishment and detailed functional and molecular genetic characterisation of a novel sacral chordoma cell line, MUG-Chor1 . Int J Oncol

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Isaac O. Karikari, Christopher L. Gilchrist, Liufang Jing, David A. Alcorta, Jun Chen, William J. Richardson, Mostafa A. Gabr, Richard D. Bell, Michael J. Kelley, Carlos A. Bagley and Lori A. Setton

, Yang W , Choy E , : Establishment and characterization of a novel chordoma cell line: CH22 . J Orthop Res 30 : 1666 – 1673 , 2012 13 McMaster ML , Goldstein AM , Bromley CM , Ishibe N , Parry DM : Chordoma: incidence and survival patterns in the United States, 1973–1995 . Cancer Causes Control 12 : 1 – 11 , 2001 14 Presneau N , Shalaby A , Ye H , Pillay N , Halai D , Idowu B , : Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study . J Pathol

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Kimberly Hamilton, Susan Rebsamen, Shahriar Salamat and Raheel Ahmed

persistent notochordal tissue beyond embryogenesis has been hypothesized to be the pathological basis for development of chordomas. 3 Embryological derivation of chordomas from notochord is supported by their shared anatomical distribution and histological, ultrastructural, and immunohistochemical features. Expression of the transcription factor T (brachyury), a hallmark of embryonic notochord differentiation, is shared by chordomas and is hypothesized to be a key molecular factor in pathogenesis. 23 EPs are nonneoplastic, hamartoma-like lesions that arise from

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Jason M. Davies, Aaron E. Robinson, Cynthia Cowdrey, Praveen V. Mummaneni, Gregory S. Ducker, Kevan M. Shokat, Andrew Bollen, Byron Hann and Joanna J. Phillips

surgery for primary versus recurrent tumor . Int J Radiat Oncol Biol Phys 65 : 1514 – 1521 , 2006 23 Presneau N , Shalaby A , Idowu B , Gikas P , Cannon SR , Gout I , : Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway . Br J Cancer 100 : 1406 – 1414 , 2009 24 Presneau N , Shalaby A , Ye H , Pillay N , Halai D , Idowu B , : Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study . J Pathol 223 : 327 – 335 , 2011 25 Ricci