Recurrent non-random genomic alterations are the hallmarks of cancer and the characterization of these imbalances is critical to our understanding of tumorigenesis and cancer progression. We are performing Array-comparative genomic hybridization (A-CGH) on cDNA microarrays containing 42,000 elements in neuroblastoma. We are developing a novel probabilistic algorithm, called topological statistics, to increase the sensitivity of cDNA A-CGH for detecting single-copy alterations. Our method not only overcomes the shortcoming of relative low sensitivity of cDNA A-CGH but also enables a direct visualization of the statistical confidence for the observed alterations. Furthermore using probabilistic approaches and machine learning algorithms (ANNs and Support Vector Machines) to estimate the frequency of genomic imbalances in tumors of different stage and MYCN amplification status, we are attempting to identify unique patterns of genomic imbalance in all three categories. Using these approaches we identifying models of the evolution and progression of neuroblastoma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010592-05
Application #
7733099
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2008
Total Cost
$54,375
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Bilke, Sven; Chen, Qing-Rong; Wei, Jun S et al. (2008) Whole chromosome alterations predict survival in high-risk neuroblastoma without MYCN amplification. Clin Cancer Res 14:5540-7
Wei, Jun S; Badgett, Thomas C; Khan, Javed (2008) New Technologies for Diagnosing Pediatric Tumors Expert Opinion on Medical Diagnostics. Expert Opin Med Diagn 2:1205-1219
Kowalska, A; Brunner, B; Bozsaky, E et al. (2008) Sequence based high resolution chromosomal CGH. Cytogenet Genome Res 121:1-6
Chen, Qing-Rong; Bilke, Sven; Wei, Jun S et al. (2006) Increased WSB1 copy number correlates with its over-expression which associates with increased survival in neuroblastoma. Genes Chromosomes Cancer 45:856-62
Bilke, Sven; Chen, Qing-Rong; Whiteford, Craig C et al. (2005) Detection of low level genomic alterations by comparative genomic hybridization based on cDNA micro-arrays. Bioinformatics 21:1138-45
Chen, Qing-Rong; Bilke, Sven; Khan, Javed (2005) High-resolution cDNA microarray-based comparative genomic hybridization analysis in neuroblastoma. Cancer Lett 228:71-81
Bilke, Sven; Chen, Qing-Rong; Westerman, Frank et al. (2005) Inferring a tumor progression model for neuroblastoma from genomic data. J Clin Oncol 23:7322-31
Chen, Qing-Rong; Bilke, Sven; Wei, Jun S et al. (2004) cDNA array-CGH profiling identifies genomic alterations specific to stage and MYCN-amplification in neuroblastoma. BMC Genomics 5:70