Exploratory analysis of the copy number alterations in glioblastoma multiforme

Pablo Freire, Marco Vilela, Helena Deus, Yong Wan Kim, Dimpy Koul, Howard Colman, Kenneth D. Aldape, Oliver Bogler, W. K.Alfred Yung, Kevin Coombes, Gordon Mills, Ana T. Vasconcelos, Jonas S. Almeida

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: The Cancer Genome Atlas project (TCGA) has initiated the analysis of multiple samples of a variety of tumor types, starting with glioblastoma multiforme. The analytical methods encompass genomic and transcriptomic information, as well as demographic and clinical data about the sample donors. The data create the opportunity for a systematic screening of the components of the molecular machinery for features that may be associated with tumor formation. The wealth of existing mechanistic information about cancer cell biology provides a natural reference for the exploratory exercise. Methodology/Principal Findings: Glioblastoma multiforme DNA copy number data was generated by The Cancer Genome Atlas project for 167 patients using 227 aCGH experiments, and was analyzed to build a catalog of aberrant regions. Genome screening was performed using an information theory approach in order to quantify aberration as a deviation from a centrality without the bias of untested assumptions about its parametric nature. A novel Cancer Genome Browser software application was developed and is made public to provide a user-friendly graphical interface in which the reported results can be reproduced. The application source code and stand alone executable are available at http://code.google.com/p/cancergenome and http://bioinformaticstation.org, respectively. Conclusions/Significance: The most important known copy number alterations for glioblastoma were correctly recovered using entropy as a measure of aberration. Additional alterations were identified in different pathways, such as cell proliferation, cell junctions and neural development. Moreover, novel candidates for oncogenes and tumor suppressors were also detected. A detailed map of aberrant regions is provided.

Original languageEnglish (US)
Article numbere4076
JournalPLoS One
Volume3
Issue number12
DOIs
StatePublished - Dec 30 2008
Externally publishedYes

Fingerprint

Glioblastoma
Genes
Tumors
neoplasms
Aberrations
Neoplasms
Screening
Genome
genome
Cytology
Atlases
Information theory
Cell proliferation
Graphical user interfaces
Application programs
intercellular junctions
screening
Machinery
Entropy
neurodevelopment

ASJC Scopus subject areas

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

Cite this

Freire, P., Vilela, M., Deus, H., Kim, Y. W., Koul, D., Colman, H., ... Almeida, J. S. (2008). Exploratory analysis of the copy number alterations in glioblastoma multiforme. PLoS One, 3(12), [e4076]. https://doi.org/10.1371/journal.pone.0004076

Exploratory analysis of the copy number alterations in glioblastoma multiforme. / Freire, Pablo; Vilela, Marco; Deus, Helena; Kim, Yong Wan; Koul, Dimpy; Colman, Howard; Aldape, Kenneth D.; Bogler, Oliver; Yung, W. K.Alfred; Coombes, Kevin; Mills, Gordon; Vasconcelos, Ana T.; Almeida, Jonas S.

In: PLoS One, Vol. 3, No. 12, e4076, 30.12.2008.

Research output: Contribution to journalArticle

Freire, P, Vilela, M, Deus, H, Kim, YW, Koul, D, Colman, H, Aldape, KD, Bogler, O, Yung, WKA, Coombes, K, Mills, G, Vasconcelos, AT & Almeida, JS 2008, 'Exploratory analysis of the copy number alterations in glioblastoma multiforme', PLoS One, vol. 3, no. 12, e4076. https://doi.org/10.1371/journal.pone.0004076
Freire P, Vilela M, Deus H, Kim YW, Koul D, Colman H et al. Exploratory analysis of the copy number alterations in glioblastoma multiforme. PLoS One. 2008 Dec 30;3(12). e4076. https://doi.org/10.1371/journal.pone.0004076
Freire, Pablo ; Vilela, Marco ; Deus, Helena ; Kim, Yong Wan ; Koul, Dimpy ; Colman, Howard ; Aldape, Kenneth D. ; Bogler, Oliver ; Yung, W. K.Alfred ; Coombes, Kevin ; Mills, Gordon ; Vasconcelos, Ana T. ; Almeida, Jonas S. / Exploratory analysis of the copy number alterations in glioblastoma multiforme. In: PLoS One. 2008 ; Vol. 3, No. 12.
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