B59
Evaluation of der(1;16)(q10;p10) chromosome rearrangement in breast cancer
Jasbani Dayal, Alastair Thompson, Mark Sales, Colin Purdie, David Kellock, Michael Boylan, Gordon Hislop, Norman Pratt
University of Dundee, UK
Previous studies involving conventional cytogenetic and comparative genomic hybridisation (CGH) techniques have reported several chromosomal abnormalities in breast cancer. In particular it is hypothesised that the der(1;16)(q10;p10) translocation is an early event in breast cancer and is associated with low chromosomal instability (CIN) and better patient outcome. Conversely, abnormalities of chromosome 17, including p53 mutation and HER2 gene amplification are associated with a higher level of genetic instability, high CIN and poor patient outcome. The aim of our study was to test this hypothesis in the context of overall chromosomal change as assessed by array CGH, fluorescent in situ hybridisation (FISH) and flow cytometry (FCM). Epithelial cells from 50 formalin fixed paraffin embedded (FFPE) tissue sections provided by Tayside Tissue Bank, were first flow sorted using a FACSVantage cell sorter. DNA was extracted according to the Qaigen protocol and hybridised to 4 x 44 K Agilent arrays. Slides were scanned using the Innopsys Innoscan 900 array scanner and analysed using Nexus (version 3.1) software.
Overall and consistent with the literature, abnormalities of chromosome 1q, 8p, 8q, 11q, 16q, 17p and 17q were common. When the tumours were categorised into low and high CIN, 12 low CIN and 11 high CIN tumours had a CGH profile consistent with the der(1;16)(q10;p10) chromosome. However, CGH alone can only confirm a copy number change indicative of the der(1;16)(q10;p10) rearrangement. Therefore, fluorescent in situ hybridisation (FISH) has been employed to definitely confirm or exclude co-localisation of chromosomes 1 and 16 centromeres associated with this rearrangement. In turn, we hope to be able to properly assess the clinical significance of the der(1;16)(q10;p10) rearrangement in breast cancer.
