Article type: Research Article
Authors: Kuijper, Arno | Snijders, Antoine M.; | Berns, Els M.J.J. | Kuenen-Boumeester, Vibeke | van der Wall, Elsken | Albertson, Donna G.; ; | van Diest, Paul J.;
Affiliations: Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands | Cancer Research Institute, University of California San Francisco, San Francisco, CA, USA | Comprehensive Cancer Centre, University of California San Francisco, San Francisco, CA, USA | Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands | Department of Pathology, Erasmus MC, Rotterdam, The Netherlands | Division of Internal Medicine and Dermatology, University Medical Centre Utrecht, Utrecht, The Netherlands | Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA
Note: [] Corresponding author: Paul J. van Diest, MD, PhD, Professor of Pathology, Department of Pathology, University Medical Centre Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. Tel.: +31 30 250 6565; Fax: +31 30 254 4990; E-mail: P.J.vanDiest@umcutrecht.nl.
Abstract: Breast phyllodes tumour (PT) is a rare fibroepithelial tumour. The genetic alterations contributing to its tumorigenesis are largely unknown. To identify genomic regions involved in pathogenesis and progression of PTs we obtained genome-wide copy number profiles by array comparative genomic hybridization (CGH). DNA was isolated from fresh-frozen tissue samples. 11 PTs and 3 fibroadenomas, a frequently occurring fibroepithelial breast tumour, were analyzed. Arrays composed of 2464 genomic clones were used, providing a resolution of ~1.4 Mb across the genome. Each clone contains at least one STS for linkage to the human genome sequence. No copy number changes were detected in fibroadenomas. On the other hand, 10 of 11 PT (91%) showed DNA copy number alterations. The mean number of chromosomal events in PT was 5.5 (range 0–16) per case. A mean of 2.0 gains (range 0–10) and 3.0 losses (range 0–9) was seen per case of PT. Three cases showed amplifications. DNA copy number change was not related to PT grade. We observed recurrent loss on chromosome 1q, 4p, 10, 13q, 15q, 16, 17p, 19 and X. Recurrent copy number gain was seen on 1q, 2p, 3q, 7p, 8q, 16q, 20. In this study we used array CGH for genomic profiling of fibroepithelial breast tumours. Whereas most PT showed chromosomal instability, fibroadenomas lacked copy number changes. Some copy number aberrations had not previously been associated with PT. Several well-known cancer related genes, such as TP53 and members of the Cadherin, reside within the recurrent regions of copy number alteration. Since copy number change was found in all benign PT, genomic instability may be an early event in PT genesis.
Keywords: Breast, phyllodes tumour, fibroadenoma, array CGH
DOI: 10.3233/CLO-2009-0457
Journal: Analytical Cellular Pathology, vol. 31, no. 1, pp. 31-39, 2009
