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Current Reviews in Musculoskeletal Medicine
Published in: Current Reviews in Musculoskeletal Medicine 4/2015

01-12-2015 | Orthopedic Oncology: New Concepts and Techniques (JH Schwab, Section Editor)

Chordoma: an update on the pathophysiology and molecular mechanisms

Authors: Xin Sun, Francis Hornicek, Joseph H. Schwab

Published in: Current Reviews in Musculoskeletal Medicine | Issue 4/2015

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Abstract

Chordoma is a rare low-grade primary malignant skeletal tumor, which is presumed to derive from notochord remnants. The pathogenesis of chordoma has not been fully elucidated. However, recent advances in the molecular biology studies have identified brachyury underlying the initiation and progression of chordoma cells. More efforts have been made on accumulating evidence of the notochordal origin of chordoma, discovering signaling pathways and identifying crucial targets in chordomagenesis. In this review, we summarize the most recent research findings and focus on the pathophysiology and molecular mechanisms of chordoma.
Literature
1.
Walcott BP, Nahed BV, Mohyeldin A, et al. Chordoma: current concepts, management, and future directions. Lancet Oncol. 2012;13(2):e69–76.CrossRefPubMed
2.
Bjornsson J, Wold LE, Ebersold MJ, et al. Chordoma of the mobile spine. A clinicopathologic analysis of 40 patients. Cancer. 1993;71(3):735–40.CrossRefPubMed
3.•
Yakkioui Y, van Overbeeke JJ, Santegoeds R, et al. Chordoma: the entity. Biochim Biophys Acta. 2014;1846(2):655–69.PubMed
4.
Ferraresi V, Nuzzo C, Zoccali C, et al. Chordoma: clinical characteristics, management and prognosis of a case series of 25 patients. BMC Cancer. 2010;10:22.PubMedCentralCrossRefPubMed
5.
6.
Wiacek MP, Kaczmarek K, Sulewski A, et al. Unusual location of chordoma metastasis. Pol Orthop Traumatol. 2014;79:47–9.PubMed
7.
8.
M¨uller H, Ueber das Vorkommen von Resten der Chorda dorsalisbeiMenschennachderGeburtund ¨uber ihrVerh¨altniss zu den Gallertgeschw¨ulsten am Clivus. Zeitung F¨ur Rationelle Medizin. 1858; 2: 202.
9.
Ribbert H, Uber die Ecchondrosis Physalifora Sphenooccipitalis. Zentralblatt F¨ur Allgemeine Pathologie Und Pathologische Anatomie. 1894; 5: 457–61.
10.
Chauvel A, Taillat F, Gille O, et al. Giant vertebral notochordal rest: a new entity distinct from chordoma. Histopathology. 2005;47(6):646–9.CrossRefPubMed
11.
Choi KS, Cohn MJ, Harfe BD. Identification of nucleus pulposus precursor cells and notochordal remnants in the mouse: implications for disk degeneration and chordoma formation. Dev Dyn. 2008;237(12):3953–8.PubMedCentralCrossRefPubMed
12.
Yamaguchi T, Suzuki S, Ishiiwa H, et al. Benign notochordal cell tumors: a comparative histological study of benign notochordal cell tumors, classic chordomas, and notochordal vestiges of fetal intervertebral discs. Am J Surg Pathol. 2004;28(6):756–61.CrossRefPubMed
13.
Kreshak J, Larousserie F, Picci P, et al. Difficulty distinguishing benign notochordal cell tumor from chordoma further suggests a link between them. Cancer Imaging. 2014;14:4.PubMedCentralPubMed
14.
Aydemir E, Bayrak OF, Sahin F, et al. Characterization of cancer stem-like cells in chordoma. J Neurosurg. 2012;116(4):810–20.CrossRefPubMed
15.
Hsu ea W. Identification of cancer stem cells in human chordoma, 27th annual meeting of th AANS/CNS section on disorders of the spine and peripheral nerves. J Neurosurg. 2011;30(3):A1–25.CrossRef
16.
Feng Y, Shen JK, Hornicek FJ, et al. Genomic and epigenetic instability in chordoma: current insights. Clin Cosmet Investig Dent. 2014;6:45–56.
17.
18.
19.
Kitamura Y, Sasaki H, Kimura T, et al. Molecular and clinical risk factors for recurrence of skull base chordomas: gain on chromosome 2p, expression of brachyury, and lack of irradiation negatively correlate with patient prognosis. J Neuropathol Exp Neurol. 2013;72(9):816–23.CrossRefPubMed
20.
Bayrakli F, Guney I, Kilic T, et al. New candidate chromosomal regions for chordoma development. Surg Neurol. 2007;68(4):425–30. discussion 430.CrossRefPubMed
21.
Walter BA, Begnami M, Valera VA, et al. Gain of chromosome 7 by chromogenic in situ hybridization (CISH) in chordomas is correlated to c-MET expression. J Neurooncol. 2011;101(2):199–206.CrossRefPubMed
22.
23.
Rinner B, Weinhaeusel A, Lohberger B, et al. Genomic instability and characteristic DNA methylation pattern in chordoma. In VIRCHOWS ARCHIV. 2013. Springer, New York.
24.
Choy E, MacConaill LE, Cote GM, et al. Genotyping cancer-associated genes in chordoma identifies mutations in oncogenes and areas of chromosomal loss involving CDKN2A, PTEN, and SMARCB1. PLoS One. 2014;9(7):e101283.PubMedCentralCrossRefPubMed
25.
Kaloostian PE, Gokaslan ZL. Understanding the cell cycle in the pathophysiology of chordomas: a molecular look. World Neurosurg. 2014;82(1–2):e135–7.CrossRefPubMed
26.
Barresi V, Ieni A, Branca G, et al. Brachyury: a diagnostic marker for the differential diagnosis of chordoma and hemangioblastoma versus neoplastic histological mimickers. Dis Markers. 2014;2014:514753.PubMedCentralCrossRefPubMed
27.
Vujovic S, Henderson S, Presneau N, et al. Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol. 2006;209(2):157–65.CrossRefPubMed
28.
Nibu Y, Jose-Edwards DS, Di Gregorio A. From notochord formation to hereditary chordoma: the many roles of brachyury. Biomed Res Int. 2013;2013:826435.PubMedCentralCrossRefPubMed
29.
Cates JM, Itani DM, Coffin CM, et al. The sonic hedgehog pathway in chordoid tumours. Histopathology. 2010;56(7):978–9.CrossRefPubMed
30.
Kozmikova I, Candiani S, Fabian P, et al. Essential role of Bmp signaling and its positive feedback loop in the early cell fate evolution of chordates. Dev Biol. 2013;382(2):538–54.CrossRefPubMed
31.
32.
Naka T, Boltze C, Kuester D, et al. Alterations of G1-S checkpoint in chordoma: the prognostic impact of p53 overexpression. Cancer. 2005;104(6):1255–63.CrossRefPubMed
33.
Yakkioui Y, Temel Y, Creytens D, et al. A comparison of cell-cycle markers in skull base and sacral chordomas. World Neurosurg. 2014;82(1–2):e311–8.CrossRefPubMed
34.
Wynford-Thomas D. P53 in tumour pathology: can we trust immunocytochemistry? J Pathol. 1992;166(4):329–30.CrossRefPubMed
35.
Hu Y, Mintz A, Shah SR, et al. The FGFR/MEK/ERK/brachyury pathway is critical for chordoma cell growth and survival. Carcinogenesis. 2014;35(7):1491–9.PubMedCentralCrossRefPubMed
36.
Alholle A, Brini AT, Bauer J, et al. Genome-wide DNA methylation profiling of recurrent and non-recurrent chordomas. Epigenetics. 2015;10(3):213–20.CrossRefPubMed
37.
Kulis M, Queiros AC, Beekman R, et al. Intragenic DNA methylation in transcriptional regulation, normal differentiation and cancer. Biochim Biophys Acta. 2013;1829(11):1161–74.CrossRefPubMed
38.
Marucci G, Morandi L, Mazzatenta D, et al. MGMT promoter methylation status in clival chordoma. J Neurooncol. 2014;118(2):271–6.CrossRefPubMed
39.
40.
41.
Duan Z, Choy E, Nielsen GP, et al. Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in Met expression. J Orthop Res. 2010;28(6):746–52.PubMed
42.
Bayrak OF, Gulluoglu S, Aydemir E, et al. MicroRNA expression profiling reveals the potential function of microRNA-31 in chordomas. J Neurooncol. 2013;115(2):143–51.CrossRefPubMed
43.
Zou MX, Huang W, Wang XB, et al. Identification of miR-140-3p as a marker associated with poor prognosis in spinal chordoma. Int J Clin Exp Pathol. 2014;7(8):4877–85.PubMedCentralPubMed
44.
Zhang Y, Schiff D, Park D, et al. MicroRNA-608 and microRNA-34a regulate chordoma malignancy by targeting EGFR, Bcl-xL and MET. PLoS One. 2014;9(3):e91546.PubMedCentralCrossRefPubMed
45.
46.
Zou MX, Huang W, Wang XB, et al., Reduced expression of miRNA-1237-3p associated with poor survival of spinal chordoma patients. Eur Spine J. 2015.
47.
48.
Tamborini E, Miselli F, Negri T, et al. Molecular and biochemical analyses of platelet-derived growth factor receptor (PDGFR) B, PDGFRA, and KIT receptors in chordomas. Clin Cancer Res. 2006;12(23):6920–8.CrossRefPubMed
49.
Tamborini E, Virdis E, Negri T, et al. Analysis of receptor tyrosine kinases (RTKs) and downstream pathways in chordomas. Neuro-Oncol. 2010;12(8):776–89.PubMedCentralCrossRefPubMed
50.
de Castro CV, Guimaraes G, Aguiar Jr S, et al. Tyrosine kinase receptor expression in chordomas: phosphorylated AKT correlates inversely with outcome. Hum Pathol. 2013;44(9):1747–55.CrossRefPubMed
51.
52.
53.
Schwab J, Antonescu C, Boland P, et al. Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma. Anticancer Res. 2009;29(6):1867–71.PubMed
54.
Chen K, Mo J, Zhou M, et al. Expression of PTEN and mTOR in sacral chordoma and association with poor prognosis. Med Oncol. 2014;31(4):886.CrossRefPubMed
55.
Burger A, Vasilyev A, Tomar R, et al. A zebrafish model of chordoma initiated by notochord-driven expression of HRASV12. Dis Model Mech. 2014;7(7):907–13.PubMedCentralCrossRefPubMed
56.
Davies JM, Robinson AE, Cowdrey C, et al. Generation of a patient-derived chordoma xenograft and characterization of the phosphoproteome in a recurrent chordoma. J Neurosurg. 2014;120(2):331–6.CrossRefPubMed
57.
Karikari IO, Gilchrist CL, Jing L, et al. Molecular characterization of chordoma xenografts generated from a novel primary chordoma cell source and two chordoma cell lines. J Neurosurg Spine. 2014;21(3):386–93.PubMedCentralCrossRefPubMed
58.
59.
Trucco MM, Awad O, Wilky BA, et al. A novel chordoma xenograft allows in vivo drug testing and reveals the importance of NF-kappaB signaling in chordoma biology. PLoS One. 2013;8(11):e79950.PubMedCentralCrossRefPubMed
Metadata
Title
Chordoma: an update on the pathophysiology and molecular mechanisms
Authors
Xin Sun
Francis Hornicek
Joseph H. Schwab
Publication date
01-12-2015
Publisher
Springer US
Published in
Current Reviews in Musculoskeletal Medicine / Issue 4/2015
Electronic ISSN: 1935-9748
DOI
https://doi.org/10.1007/s12178-015-9311-x

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