Update on the Cytogenetics and Molecular Genetics of Chordoma
<p>Abstract</p> <p>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 inter...
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| Format: | Article |
| Language: | English |
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BMC
2005-02-01
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| Series: | Hereditary Cancer in Clinical Practice |
| Subjects: | |
| Online Access: | http://www.hccpjournal.com/content/3/1/29 |
| _version_ | 1811247923282837504 |
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| author | Larizza Lidia Mortini Pietro Riva Paola |
| author_facet | Larizza Lidia Mortini Pietro Riva Paola |
| author_sort | Larizza Lidia |
| collection | DOAJ |
| description | <p>Abstract</p> <p>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.</p> |
| first_indexed | 2024-04-12T15:17:59Z |
| format | Article |
| id | doaj.art-f97309d51d3a4c32a29f68bfc6d85438 |
| institution | Directory Open Access Journal |
| issn | 1897-4287 |
| language | English |
| last_indexed | 2024-04-12T15:17:59Z |
| publishDate | 2005-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditary Cancer in Clinical Practice |
| spelling | doaj.art-f97309d51d3a4c32a29f68bfc6d854382022-12-22T03:27:33ZengBMCHereditary Cancer in Clinical Practice1897-42872005-02-0131294110.1186/1897-4287-3-1-29Update on the Cytogenetics and Molecular Genetics of ChordomaLarizza LidiaMortini PietroRiva Paola<p>Abstract</p> <p>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.</p>http://www.hccpjournal.com/content/3/1/29chordoma1p36 LOH7q33 linkageTSC association |
| spellingShingle | Larizza Lidia Mortini Pietro Riva Paola Update on the Cytogenetics and Molecular Genetics of Chordoma Hereditary Cancer in Clinical Practice chordoma 1p36 LOH 7q33 linkage TSC association |
| title | Update on the Cytogenetics and Molecular Genetics of Chordoma |
| title_full | Update on the Cytogenetics and Molecular Genetics of Chordoma |
| title_fullStr | Update on the Cytogenetics and Molecular Genetics of Chordoma |
| title_full_unstemmed | Update on the Cytogenetics and Molecular Genetics of Chordoma |
| title_short | Update on the Cytogenetics and Molecular Genetics of Chordoma |
| title_sort | update on the cytogenetics and molecular genetics of chordoma |
| topic | chordoma 1p36 LOH 7q33 linkage TSC association |
| url | http://www.hccpjournal.com/content/3/1/29 |
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