Genomic profiling by array comparative genomic hybridization reveals novel DNA copy number changes in breast phyllodes tumours.
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.
Kuijper
Arno
A
Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Snijders
Antoine M
AM
Berns
Els M J J
EM
Kuenen-Boumeester
Vibeke
V
van der Wall
Elsken
E
Albertson
Donna G
DG
van Diest
Paul J
PJ
D001943:Breast Neoplasms / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D003557:Phyllodes Tumor / Q000235:genetics*