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Updated: Jun 1, 2026
08:16
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Recurrent chromosomal copy number alterations in sporadic chordomas
Long Phi Le1, G Petur Nielsen, Andrew Eric Rosenberg
1Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. lple@partners.org
Plos One
|May 24, 2011
Summary
Chordoma tumors frequently lose key genes like CDKN2A and PTEN. These copy number losses, not promoter methylation, are crucial for chordoma development and may offer therapeutic targets.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Chordoma pathogenesis molecular events remain unclear, especially copy number alterations.
- Understanding these changes could improve chordoma classification and therapy.
Purpose of the Study:
- To analyze copy number alterations in sporadic chordomas.
- To investigate the role of specific gene losses (CDKN2A, PTEN) in chordoma development.
Main Methods:
- Array comparative genomic hybridization (CGH) on 21 sporadic chordomas.
- Immunohistochemistry, methylation-specific PCR, and quantitative real-time PCR for validation.
Main Results:
- Frequent copy number losses observed on chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18.
- Loss of CDKN2A (80%) and PTEN (80%) were common, with homozygous deletions for CDKN2A in 30%.
- Loss of CDKN2A and PTEN expression was not linked to promoter methylation and T/brachyury amplification was rare.
Conclusions:
- Deficiency in CDKN2A and PTEN expression is a significant aspect of chordoma pathogenesis.
- Sporadic chordomas may utilize alternative mechanisms beyond copy number gain for proliferation, potentially independent of T/brachyury amplification.
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