title: From notochord formation to hereditary chordoma: the many roles of Brachyury.
abstract: Chordoma is a rare, but often malignant, bone cancer that preferentially affects the axial skeleton and the skull base. These tumors are both sporadic and hereditary and appear to occur more frequently after the fourth decade of life; however, modern technologies have increased the detection of pediatric chordomas. Chordomas originate from remnants of the notochord, the main embryonic axial structure that precedes the backbone, and share with notochord cells both histological features and the expression of characteristic genes. One such gene is Brachyury, which encodes for a sequence-specific transcription factor. Known for decades as a main regulator of notochord formation, Brachyury has recently gained interest as a biomarker and causative agent of chordoma, and therefore as a promising therapeutic target. Here, we review the main characteristics of chordoma, the molecular markers, and the clinical approaches currently available for the early detection and possible treatment of this cancer. In particular, we report on the current knowledge of the role of Brachyury and of its possible mechanisms of action in both notochord formation and chordoma etiogenesis.
authors: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA. yun2001@med.cornell.edu
authors: Yutaka
authors: Y
authors: Nibu
authors: Diana S
authors: DS
authors: José-Edwards
authors: Anna
authors: A
authors: Di Gregorio
mesh_terms: D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D002817:Chordoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D009672:Notochord / Q000196:embryology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein
references: Blood. 2008 Feb 15;111(4):1933-41
references: 18042803
references: Genes Dev. 2004 Jul 15;18(14):1725-36
references: 15231714
references: EMBO J. 1995 Oct 2;14(19):4763-72
references: 7588606
references: J Bone Joint Surg Am. 2010 May;92(5):1231-40
references: 20439670
references: Int J Oncol. 2012 Oct;41(4):1405-10
references: 22824918
references: Evol Dev. 2008 Jan-Feb;10(1):37-51
references: 18184356
references: Neurosurgery. 2006 Aug;59(2):230-7; discussion 230-7
references: 16883163
references: Mod Pathol. 2008 Dec;21(12):1461-9
references: 18820665
references: Cancer Genet Cytogenet. 2005 Jul 1;160(1):15-21
references: 15949565
references: Cell Cycle. 2011 Nov 1;10(21):3645-51
references: 22033440
references: J Cell Biol. 2003 Sep 15;162(6):1017-29
references: 12963707
references: Br J Cancer. 2009 May 5;100(9):1406-14
references: 19401700
references: Jpn J Clin Oncol. 1998 Dec;28(12):766-71
references: 9879297
references: Nature. 1990 Feb 15;343(6259):657-9
references: 1689462
references: Bioessays. 2001 Sep;23(9):788-94
references: 11536291
references: Dev Biol. 2001 Jun 1;234(1):1-12
references: 11356015
references: Nature. 1995 Nov 9;378(6553):150-7
references: 7477317
references: PLoS One. 2012;7(12):e52020
references: 23284858
references: Clin Cancer Res. 2012 Jul 15;18(14):3868-79
references: 22611028
references: Dev Genes Evol. 1997 May;207(1):1-11
references: 20607475
references: Am J Clin Pathol. 1995 Mar;103(3):271-9
references: 7532910
references: Arch Pathol Lab Med. 2010 Aug;134(8):1181-7
references: 20670140
references: Crit Rev Oncog. 2013;18(1-2):43-73
references: 23237552
references: Curr Oncol Rep. 2007 Jul;9(4):323-7
references: 17588358
references: Development. 2009 Nov;136(21):3679-89
references: 19820186
references: Osteoarthritis Cartilage. 2006 Jan;14(1):30-8
references: 16188469
references: Dev Genes Evol. 2003 Oct;213(10):492-9
references: 13680223
references: Development. 1996 Aug;122(8):2427-35
references: 8756288
references: EMBO J. 1993 Aug;12(8):3211-20
references: 8344258
references: Dev Biol. 2007 Feb 1;302(1):92-103
references: 17022960
references: Development. 1999 Sep;126(18):3991-4003
references: 10457009
references: Development. 2010 May;137(10):1613-23
references: 20392745
references: Genes Chromosomes Cancer. 2001 Nov;32(3):203-11
references: 11579460
references: Cancer Causes Control. 2001 Jan;12(1):1-11
references: 11227920
references: Int J Oncol. 2012 Feb;40(2):443-51
references: 22002331
references: Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3829-34
references: 19225104
references: Mol Biol Evol. 2011 Mar;28(3):1241-1254
references: 21087945
references: Nature. 1990 Feb 15;343(6259):617-22
references: 2154694
references: Proc Natl Acad Sci U S A. 1944 Jun 15;30(6):134-40
references: 16588636
references: Mol Biol Cell. 2011 Oct;22(20):3768-78
references: 21849473
references: Genetics. 2007 Oct;177(2):1151-61
references: 17954925
references: J Embryol Exp Morphol. 1958 Sep;6(3):424-43
references: 13575656
references: Dev Genes Evol. 2003 Jan;212(12):563-70
references: 12536320
references: Int J Hematol. 2008 Jan;87(1):39-47
references: 18224412
references: Strahlenther Onkol. 1999 Jun;175 Suppl 2:57-63
references: 10394399
references: Development. 1998 Oct;125(20):3997-4006
references: 9735361
references: Dev Biol. 2000 Aug 1;224(1):69-80
references: 10898962
references: Semin Oncol. 2012 Jun;39(3):358-66
references: 22595058
references: Development. 2007 Dec;134(23):4187-97
references: 17993466
references: Dev Dyn. 2011 Jul;240(7):1793-805
references: 21594950
references: Dev Biol. 2010 Mar 1;339(1):212-22
references: 20036227
references: J Cell Sci. 2010 Jul 15;123(Pt 14):2453-63
references: 20592183
references: Arthritis Rheum. 2007 Nov;56(11):3693-705
references: 17968906
references: Development. 1996 Dec;122(12):3707-18
references: 9012492
references: Vaccine. 2011 Nov 21;29(50):9361-7
references: 22001882
references: Spine (Phila Pa 1976). 2010 Jun 1;35(13):1257-64
references: 20461036
references: J Bone Joint Surg Am. 2012 Feb 15;94(4):356-63
references: 22336975
references: Cancer. 1993 Aug 1;72(3):714-8
references: 8334623
references: Eur Radiol. 1998;8(9):1677-9
references: 9866786
references: Case Rep Oncol Med. 2012;2012:693137
references: 23091759
references: Dev Biol. 2002 Oct 1;250(1):112-27
references: 12297100
references: Dev Biol. 2006 Jul 1;295(1):128-40
references: 16678811
references: Anticancer Drugs. 2009 Nov;20(10):953-5
references: 19730087
references: Genes Dev. 1994 Sep 15;8(18):2137-50
references: 7958884
references: Bioessays. 2006 Apr;28(4):413-20
references: 16547957
references: BMC Cancer. 2012 Aug 29;12:377
references: 22931165
references: Genetics. 1998 Nov;150(3):1125-31
references: 9799264
references: EMBO J. 1994 Oct 3;13(19):4469-81
references: 7925289
references: J Bone Joint Surg Am. 1981 Mar;63(3):501-5
references: 7009618
references: Am J Hum Genet. 2001 Aug;69(2):454-60
references: 11452362
references: Development. 2006 Aug;133(15):2855-64
references: 16835438
references: Dev Biol. 1995 Apr;168(2):406-15
references: 7729577
references: Mol Cancer Res. 2010 Nov;8(11):1558-67
references: 20881009
references: Hum Pathol. 1991 Jan;22(1):22-8
references: 1702083
references: Nat Genet. 2009 Nov;41(11):1176-8
references: 19801981
references: Spine (Phila Pa 1976). 2009 Jun 15;34(14):E493-7
references: 19525829
references: Skeletal Radiol. 2007 Jan;36(1):59-65
references: 16810540
references: Bioessays. 1998 Jan;20(1):9-19
references: 9504043
references: J Neuroradiol. 1991;18(3):267-76
references: 1765812
references: Dev Biol. 2001 Nov 1;239(1):132-47
references: 11784024
references: Dis Model Mech. 2012 Jan;5(1):73-82
references: 22028328
references: J Pathol. 2006 Jun;209(2):143-6
references: 16604512
references: Int J Cancer. 2005 Sep 1;116(3):487-91
references: 15818627
references: Dev Dyn. 2005 May;233(1):1-19
references: 15765512
references: Genes Dev. 1999 Jun 15;13(12):1519-23
references: 10385620
references: Dev Dyn. 2007 Jul;236(7):1806-19
references: 17576134
references: Arch Pathol Lab Med. 2010 Feb;134(2):283-8
references: 20121620
references: Genes Dev. 1993 Feb;7(2):197-203
references: 8436292
references: Radiat Oncol. 2011 Sep 14;6:116
references: 21914223
references: Cancer. 1984 Jun 1;53(11):2574-8
references: 6713355
references: Int J Radiat Oncol Biol Phys. 1985 Jul;11(7):1339-47
references: 4008290
references: Dev Cell. 2008 Jul;15(1):121-33
references: 18606146
references: Cell. 2011 Jan 7;144(1):27-40
references: 21215367
references: Biomed Eng Online. 2007 Sep 06;6:33
references: 17822560
references: Development. 1998 Jul;125(13):2511-20
references: 9609834
references: Development. 1991 Nov;113(3):913-7
references: 1821859
references: Science. 2006 May 26;312(5777):1183-7
references: 16728634
references: Genomics. 2001 Apr 15;73(2):211-22
references: 11318611
references: J Clin Pathol. 1962 Mar;15:116-25
references: 13895301
references: Clin Neuropathol. 1985 Mar-Apr;4(2):77-86
references: 3995810
references: J Neurosurg. 2012 Apr;116(4):810-20
references: 22283189
references: Childs Nerv Syst. 2010 Jun;26(6):835-40
references: 20094721
references: Cell Mol Life Sci. 2012 Oct;69(20):3429-56
references: 22945800
references: Dev Biol. 2009 Apr 15;328(2):561-74
references: 19217895
references: Pathologica. 1993 Nov-Dec;85(1100):755-60
references: 7513394
references: PLoS One. 2012;7(3):e33346
references: 22479388
references: Cell. 1991 Oct 4;67(1):79-87
references: 1717160
references: Onkologie. 2006 Dec;29(12):572-4
references: 17202828
references: J Orthop Res. 2012 Oct;30(10):1666-73
references: 22504929
references: Spine (Phila Pa 1976). 2006 Feb 15;31(4):493-503
references: 16481964
references: J Biol Chem. 1999 Jul 16;274(29):20489-98
references: 10400677
references: Development. 1994 Apr;120(4):1009-15
references: 7600949
references: Dev Growth Differ. 2001 Feb;43(1):1-11
references: 11148447
references: Biochimie. 2004 Aug;86(8):523-31
references: 15388229
references: Skull Base. 2008 Nov;18(6):395-9
references: 19412409
references: Cancer. 2004 Nov 1;101(9):2086-97
references: 15372471
references: J Biol Chem. 2006 Sep 1;281(35):25416-24
references: 16772300
references: Pediatr Dev Pathol. 2010 Jan-Feb;13(1):9-17
references: 19348512
references: FEBS Lett. 1997 Jun 9;409(2):201-6
references: 9202145
references: Evol Dev. 2012 Jan-Feb;14(1):56-75
references: 23016975
references: Nature. 1993 Aug 12;364(6438):582-3
references: 8350918
references: J Neurosurg. 2011 Oct;115(4):760-9
references: 21699479
references: J Clin Invest. 2010 Feb;120(2):533-44
references: 20071775
references: Clin Imaging. 2004 May-Jun;28(3):187-90
references: 15158222
references: Pathol Res Pract. 2011 May 15;207(5):327-31
references: 21397407
references: J Pathol. 2006 Jun;209(2):157-65
references: 16538613
references: Diagn Mol Pathol. 1995 Sep;4(3):162-73
references: 7493135
references: Mol Cell Biol. 2004 Jun;24(12):5257-68
references: 15169890
references: Development. 1998 Oct;125(19):3887-94
references: 9729496
references: Clin Cancer Res. 2006 Dec 1;12(23):6920-8
references: 17145809
references: Development. 2010 Apr;137(7):1127-35
references: 20215349
references: PLoS One. 2011;6(12):e28394
references: 22164283
references: Development. 1999 Dec;126(24):5599-609
references: 10572037
references: Int J Dev Biol. 2000 Apr;44(3):279-88
references: 10853824
references: Development. 2000 May;127(10):2227-38
references: 10769246
references: J Pathol. 2012 Nov;228(3):274-85
references: 22847733
references: Nat Genet. 2012 Nov;44(11):1185-7
references: 23064415
references: Genesis. 2008 Nov;46(11):697-710
references: 18802963
references: Cancer Immunol Immunother. 2009 Mar;58(3):339-49
references: 18641983
references: Br J Cancer. 2007 Jan 15;96(1):180-1
references: 17213828
references: Dev Biol. 2003 Aug 15;260(2):352-61
references: 12921737
references: Dev Genes Evol. 2010 Dec;220(9-10):251-62
references: 21082201
references: Dev Biol. 2002 Jun 1;246(1):191-208
references: 12027442
references: Development. 1992 Dec;116(4):1021-32
references: 1295726
references: Surg Neurol. 2007 Oct;68(4):425-30; discussion 430
references: 17714767
references: Br J Radiol. 2011 Dec;84 Spec No 1:S48-54
references: 21427182
references: Dev Biol. 1997 Sep 15;189(2):161-73
references: 9299111
references: Orthopedics. 2004 Dec;27(12):1256-63; quiz 1264-5
references: 15633956
references: Front Biosci. 1999 Jun 15;4:D528-32
references: 10369808
references: Development. 1995 May;121(5):1351-9
references: 7789266
references: Dev Biol. 2007 Jun 15;306(2):870-82
references: 17459364
references: J Pathol. 2011 Feb;223(3):327-35
references: 21171078
references: Am J Surg Pathol. 2008 Apr;32(4):572-80
references: 18301055
references: Mech Dev. 1998 Jul;75(1-2):139-43
references: 9739128
references: Dev Biol. 1995 Nov;172(1):242-52
references: 7589804
references: Oncologist. 2007 Nov;12(11):1344-50
references: 18055855
references: Development. 1995 Dec;121(12):4283-91
references: 8575328
references: Genome Res. 1996 Mar;6(3):226-33
references: 8963900
references: Clin Cancer Res. 2007 Apr 15;13(8):2471-8
references: 17438107
references: FEBS Lett. 2005 Sep 12;579(22):5024-8
references: 16122738
references: Development. 2002 Jul;129(14):3441-53
references: 12091314
references: Development. 2007 Dec;134(23):4209-18
references: 17959720
references: Development. 2004 Mar;131(6):1279-88
references: 14993185
references: Development. 1997 Feb;124(3):589-602
references: 9043074
references: Mech Dev. 2000 May;93(1-2):27-39
references: 10781937
references: Dev Biol. 2003 Dec 15;264(2):456-66
references: 14651930
references: Br J Cancer. 2008 Jan 29;98(2):434-42
references: 18071362
references: J Cell Commun Signal. 2008 Dec;2(3-4):59-65
references: 19003520
references: J Clin Oncol. 2005 May 20;23(15):3597-604
references: 15908670
references: Ann Oncol. 2009 Nov;20(11):1886-94
references: 19570961
references: Mol Cell Biol. 2008 May;28(10):3236-44
references: 18332117
references: Nature. 1997 Oct 23;389(6653):884-8
references: 9349824
references: Spine (Phila Pa 1976). 1978 Dec;3(4):351-66
references: 741243
references: Genes Dev. 2002 Feb 15;16(4):518-29
references: 11850413
references: Int J Dev Biol. 2001;45(1):219-24
references: 11291849
references: Neurosurgery. 1999 Jan;44(1):74-9; discussion 79-80
references: 9894966
references: Cell Res. 2011 Jun;21(6):911-21
references: 21423269