Chordoma is a rare mesenchymal tumour of complex biology for which only histologic and immunohistochemical criteria have been defined, but no
biomarkers predicting the clinical outcome and response to treatment have yet been recognised. We herein review the interdisciplinary information achieved by epidemiologists, neurosurgeons and basic scientists on
chordoma, usually a sporadic tumour, which also includes a small fraction of familial cases. Main focus is on the current knowledge of the genetic alterations which might pinpoint candidate genes and molecular mechanisms shared by sporadic and familiar
chordomas. Due to the scarcity of the investigated tumour specimens and the multiple
chromosome abnormalities found in tumours with aberrant karyotypes, conventional cytogenetics and Fluorescence In Situ Hybridization failed to detect recurrent
chordoma-specific chromosomal rearrangements. Genome-wide approaches such as Comparative Genomic Hybridization (CGH) are yet at an initial stage of application and should be implemented using BAC arrays either genome-wide or targeting selected genomic regions, disclosed by Loss of Heterozygosity (LOH) studies. An LOH region was shown by a systematic study on a consistent number of
chordomas to encompass 1p36, a genomic interval where a candidate gene was suggested to reside. Despite the rarity of multiplex families with
chordoma impaired linkage studies, a
chordoma locus could be mapped to chromosome 7q33 by positive lod score in three independent families. The role in chordomagenesis of the
Tuberous Sclerosis Complex (
TSC) genes has been proved, but the extent of involvement of TSC1 and TSC2 oncosuppressors in
chordoma remains to be assessed. In spite of the scarce knowledge on the genetics and molecular biology of
chordoma, recent initiation of clinical trials using
molecular-targeted therapy, should validate new molecular targets and predict the efficacy of a given
therapy. Comparative genetic and biomolecular studies should enhance the molecular taxonomy of
chordoma which might have a prognostic significance and better orient the therapeutic options.