Measurement and relevance of neuroblastoma DNA copy number changes in the post-genome era

Mosse, Yael P.; Greshock, Joel; Weber, Barbara L.; Maris, John M.

doi:10.1016/j.canlet.2005.02.052

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Volume 228, Issue 1 , Pages 83-90, 18 October 2005

Measurement and relevance of neuroblastoma DNA copy number changes in the post-genome era

Yael P. Mosse
- Division of Oncology, Children's Hospital of Philadelphia, Abramson Pediatric Research Center 902A, 3615 Civic Center Blvd, Philadelphia, PA 19104-4318, USA
- Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Joel Greshock
- Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Barbara L. Weber
- Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
John M. Maris
- Division of Oncology, Children's Hospital of Philadelphia, Abramson Pediatric Research Center 902A, 3615 Civic Center Blvd, Philadelphia, PA 19104-4318, USA
- Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- Corresponding author. Address: Division of Oncology, Children's Hospital of Philadelphia, Abramson Pediatric Research Center 902A, 3615 Civic Center Blvd, Philadelphia, PA 19104-4318, USA. Tel.: +1 215 590 2821; fax: +1 215 590 3770.

Received 7 January 2005; accepted 5 February 2005.

Abstract

The completion of the human genome sequence and the development of high throughput technology present exciting opportunities for the study of cancer cells. High-resolution analysis of chromosomal aberrations provides a global framework for understanding complex patterns in cancer cells, allowing us to ask hypothesis-driven questions. Genome-wide analysis of amplification and deletion of genomic regions is a critical step to resolving the mechanisms of neuroblastoma tumorigenesis. We used a high-resolution aCGH system that has over 4000 human BAC clones, resulting in an average coverage of 1Mb across the genome, to define whole genome copy number aberrations (CNAs) in a panel of human neuroblastoma-derived cell lines. By combining the aCGH data with meticulous regional validation studies, we showed that array CGH could reliably detect known aberrations including single copy gain or loss, that data correlate well with standard techniques used for the detection of these genetic changes, and that this technique can be used to identify novel regions of genomic imbalance.