Recurrent chromosomal copy number alterations in sporadic chordomas

Long Phi Le, G. Petur Nielsen, Andrew Rosenberg, Dafydd Thomas, Julie M. Batten, Vikram Deshpande, Joseph Schwab, Zhenfeng Duan, Ramnik J. Xavier, Francis J. Hornicek, A. John Iafrate

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recurrent copy changes were further evaluated with immunohistochemistry, methylation specific PCR, and quantitative real-time PCR. Similar to previous findings, large copy number losses, involving chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18, were more common than copy number gains. Loss of CDKN2A with or without loss of CDKN2B on 9p21.3 was observed in 16/20 (80%) unique cases of which six (30%) showed homozygous deletions ranging from 76 kilobases to 4.7 megabases. One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases. Loss of CDKN2A and PTEN expression in the majority of cases was not attributed to promoter methylation. Our sporadic chordoma cases did not show hotspot point mutations in some common cancer gene targets. Moreover, most of these sporadic tumors are not associated with T (brachyury) duplication or amplification. Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis. Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/brachyury for proliferation.

Original languageEnglish
Article numbere18846
JournalPLoS One
Volume6
Issue number5
DOIs
StatePublished - May 18 2011
Externally publishedYes

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Chordoma
neoplasms
Tumors
Methylation
methylation
pathogenesis
comparative genomic hybridization
chromosome elimination
point mutation
immunohistochemistry
Neoplasms
Chromosomes
quantitative polymerase chain reaction
Chromosomes, Human, Pair 3
Comparative Genomic Hybridization
Neoplasm Genes
promoter regions
Amplification
Point Mutation
therapeutics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Le, L. P., Nielsen, G. P., Rosenberg, A., Thomas, D., Batten, J. M., Deshpande, V., ... Iafrate, A. J. (2011). Recurrent chromosomal copy number alterations in sporadic chordomas. PLoS One, 6(5), [e18846]. https://doi.org/10.1371/journal.pone.0018846

Recurrent chromosomal copy number alterations in sporadic chordomas. / Le, Long Phi; Nielsen, G. Petur; Rosenberg, Andrew; Thomas, Dafydd; Batten, Julie M.; Deshpande, Vikram; Schwab, Joseph; Duan, Zhenfeng; Xavier, Ramnik J.; Hornicek, Francis J.; Iafrate, A. John.

In: PLoS One, Vol. 6, No. 5, e18846, 18.05.2011.

Research output: Contribution to journalArticle

Le, LP, Nielsen, GP, Rosenberg, A, Thomas, D, Batten, JM, Deshpande, V, Schwab, J, Duan, Z, Xavier, RJ, Hornicek, FJ & Iafrate, AJ 2011, 'Recurrent chromosomal copy number alterations in sporadic chordomas', PLoS One, vol. 6, no. 5, e18846. https://doi.org/10.1371/journal.pone.0018846
Le LP, Nielsen GP, Rosenberg A, Thomas D, Batten JM, Deshpande V et al. Recurrent chromosomal copy number alterations in sporadic chordomas. PLoS One. 2011 May 18;6(5). e18846. https://doi.org/10.1371/journal.pone.0018846
Le, Long Phi ; Nielsen, G. Petur ; Rosenberg, Andrew ; Thomas, Dafydd ; Batten, Julie M. ; Deshpande, Vikram ; Schwab, Joseph ; Duan, Zhenfeng ; Xavier, Ramnik J. ; Hornicek, Francis J. ; Iafrate, A. John. / Recurrent chromosomal copy number alterations in sporadic chordomas. In: PLoS One. 2011 ; Vol. 6, No. 5.
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