Bone: Chordoma

1998-09-01   Monica Miozzo 

1.Dipartimento di Medicina Ospedale San Paolo Lab. di Genetica Umana,Via di Rudin,8, 20142 Milan, Italy
2.Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands. J.V.M.G.Bovee@lumc.nl

Summary

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

Abstract

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

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.

Cytogenetics

Cytogenetics morphological

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.

Bibliography

Pubmed IDLast YearTitleAuthors
276359482017SMARCB1/INI1 Involvement in Pediatric Chordoma: A Mutational and Immunohistochemical Analysis.Antonelli M et al
81740901994Clonal chromosome aberrations in three sacral chordomas.Mertens F et al
260990102015Nuclear 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 et al
230644152012A common single-nucleotide variant in T is strongly associated with chordoma.Pillay N et al
279014922017Genomic and transcriptomic characterization of skull base chordoma.Sa JK et al
271025722016EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen.Scheipl S et al
94756101998Familial chordoma with probable autosomal dominant inheritance.Stepanek J et al
270721942016Genomic aberrations frequently alter chromatin regulatory genes in chordoma.Wang L et al
287975062017Notochordal Tumors: An Update on Molecular Pathology with Therapeutic Implications.Yamaguchi T et al

Citation

Monica Miozzo

Bone: Chordoma

Atlas Genet Cytogenet Oncol Haematol. 1998-09-01

Online version: http://atlasgeneticsoncology.org/solid-tumor/5028/bone-chordoma

Historical Card

0000-00-00 Bone: Chordoma by  Arjen Cleven,Judith Bovée 

Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands. J.V.M.G.Bovee@lumc.nl