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Bone: Chordoma

Written2017-11Arjen Cleven, Judith Bovée
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
This article is an update of :
1998-09Monica Miozzo
Dipartimento di Medicina Ospedale San Paolo Lab. di Genetica Umana,Via di Rudin,8, 20142 Milan, Italy

(Note : for Links provided by Atlas : click)


Abstract Review on Chordoma, with data on clinics, and the genes involved.


ICD-Topo C400-C403,C408-C414,C418-C419 BONES & JOINTS
ICD-Morpho 9370/3 Chordoma, NOS
Atlas_Id 5028
Phylum Bones::Chordoma
WHO/OMS Classification Bones
Note Chordoma is a malignant tumour derived from remnants of the fetal notochord; it occurs along the spinal axis, predominantly in the sphenooccipital (35%), vertebral (15%) and sacrococcygeal (50%) regions

Clinics and Pathology

Etiology Although most chordomas are sporadics, five families with chordoma occurrence have been reported, two of them displaying an autosomal dominant transmission with incomplete penetrance (MIM. *215400).
Epidemiology Chordomas accounts for 1-4% of all primary bone tumours; the sacrococcygeal lesions are more common in the fifth decade of life, whereas the sphenooccipital tumours occur predominantly in children.
Clinics Chordoma is a slowly-growing tumour, characterized by local destruction of bone and rarely distant metastatic spread.
the differential diagnosis includes renal tumours, chondrosarcomas and myxopapillary ependymoma.
Pathology Microscopically, it resembles normal fetal notochord in its different stages of development; it is composed of extremely large cells (known as physaliferous) and other small tumour cells; areas of cartilage and bone may be present.
Dedifferentiated chordoma is a biphasic tumor, with features of a chordoma NOS and an abrupt transition to a high grade undifferentiated spindle cell tumor. Chordomas express keratins and brachyury is a highly specific marker for chordoma and helps to distinguish chordoma from chondrosarcoma and clear cell renal cell carcinoma. Brachyury as well as keratins are not expressed in a dedifferentiated component.


The most common cytogenetic abnormality in chordoma is monosomy of chromosome 1 and gain of chromosome 7.

Genes involved and Proteins

Note Approximately 70% of chordomas harbour either homozygous or heterozygous loss of CDKN2A and CDKN2B. Additional copy-number gain of brachyury (gene: T (T Brachyury Transcription Factor) ) on chromosome locus 7q33 are commonly found in chordomas. In the coding region of brachyury somatic mutations have been found as well. Hotspot mutations in the tyrosine kinase receptor gene EGFR and in KRAS, NRAS, HRAS, BRAF are also described in chordomas. Furthermore, deletions and point mutations in SMARCB1 gene can be found.


SMARCB1/INI1 Involvement in Pediatric Chordoma: A Mutational and Immunohistochemical Analysis
Antonelli M, Raso A, Mascelli S, Gessi M, Nozza P, Coli A, Gardiman MP, Arcella A, Massimino M, Buttarelli FR, Giangaspero F
Am J Surg Pathol 2017 Jan;41(1):56-61
PMID 27635948
Cytogenetic, telomere, and telomerase studies in five surgically managed lumbosacral chordomas
Butler MG, Dahir GA, Hedges LK, Juliao SF, Sciadini MF, Schwartz HS
Cancer Genet Cytogenet 1995 Nov;85(1):51-7
Genomic screening for linkage in a family with autosomal dominant chordoma
Korczak JF, Kelley MJ, Allikian KA, Shah AA, Goldstein AM, Parry DM
Am J Hum Genet. 1997 ; 61 : page A400.
Clonal chromosome aberrations in three sacral chordomas
Mertens F, Kreicbergs A, Rydholm A, Willén H, Carlén B, Mitelman F, Mandahl N
Cancer Genet Cytogenet 1994 Apr;73(2):147-51
PMID 8174090
Nuclear Brachyury Expression Is Consistent in Chordoma, Common in Germ Cell Tumors and Small Cell Carcinomas, and Rare in Other Carcinomas and Sarcomas: An Immunohistochemical Study of 5229 Cases
Miettinen M, Wang Z, Lasota J, Heery C, Schlom J, Palena C
Am J Surg Pathol 2015 Oct;39(10):1305-12
PMID 26099010
A common single-nucleotide variant in T is strongly associated with chordoma
Pillay N, Plagnol V, Tarpey PS, Lobo SB, Presneau N, Szuhai K, Halai D, Berisha F, Cannon SR, Mead S, Kasperaviciute D, Palmen J, Talmud PJ, Kindblom LG, Amary MF, Tirabosco R, Flanagan AM
Nat Genet 2012 Nov;44(11):1185-7
PMID 23064415
Genomic and transcriptomic characterization of skull base chordoma
Sa JK, Lee IH, Hong SD, Kong DS, Nam DH
Oncotarget 2017 Jan 3;8(1):1321-1328
PMID 27901492
EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen
Scheipl S, Barnard M, Cottone L, Jorgensen M, Drewry DH, Zuercher WJ, Turlais F, Ye H, Leite AP, Smith JA, Leithner A, Möller P, Brüderlein S, Guppy N, Amary F, Tirabosco R, Strauss SJ, Pillay N, Flanagan AM
J Pathol 2016 Jul;239(3):320-34
PMID 27102572
Familial chordoma with probable autosomal dominant inheritance
Stepanek J, Cataldo SA, Ebersold MJ, Lindor NM, Jenkins RB, Unni K, Weinshenker BG, Rubenstein RL
Am J Med Genet 1998 Jan 23;75(3):335-6
PMID 9475610
Genomic aberrations frequently alter chromatin regulatory genes in chordoma
Wang L, Zehir A, Nafa K, Zhou N, Berger MF, Casanova J, Sadowska J, Lu C, Allis CD, Gounder M, Chandhanayingyong C, Ladanyi M, Boland PJ, Hameed M
Genes Chromosomes Cancer 2016 Jul;55(7):591-600
PMID 27072194
Notochordal Tumors: An Update on Molecular Pathology with Therapeutic Implications
Yamaguchi T, Imada H, Iida S, Szuhai K
Surg Pathol Clin 2017 Sep;10(3):637-656
PMID 28797506


This paper should be referenced as such :
Arjen Cleven, Judith Bove
Bone: Chordoma
Atlas Genet Cytogenet Oncol Haematol. 2018;22(12):520-521.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Miozzo, M. Bone: Chordoma. Atlas Genet Cytogenet Oncol Haematol. 1999;3(1):39-40.

Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]


External links

arrayMap Topo ( C40,C41) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
Disease databaseBone: Chordoma
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

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