Exploratory analysis of the copy number alterations in glioblastoma multiforme.
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.


RESULTS
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
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.
Freire
Pablo
P
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Vilela
Marco
M
Deus
Helena
H
Kim
Yong-Wan
YW
Koul
Dimpy
D
Colman
Howard
H
Aldape
Kenneth D
KD
Bogler
Oliver
O
Yung
W K Alfred
WK
Coombes
Kevin
K
Mills
Gordon B
GB
Vasconcelos
Ana T
AT
Almeida
Jonas S
JS
D055028:Comparative Genomic Hybridization; D019277:Entropy; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics