¹Cancer Genomics Program, Departments of Pathology and Oncology, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, UK

Correspondence: Dr PAW Edwards, Hutchison/MRC Research Centre, Cambridge CB2 2XZ, UK. E-mail: pawe1@cam.ac.uk

²Current address: The Animal Health Trust, Centre for Preventive Medicine, Lanwades Park, Kentford, Newmarket, CB8 7UU, UK.

³Current address: Comparative Genomics Group, Research School of Biological Sciences, The Australian National University, GPO Box 475, Canberra, ACT 2601, Australia.

⁴Current address: University of Cambridge Clinical School, Hills Road, Cambridge, UK.

Received 11 November 2005; Revised 23 January 2006; Accepted 28 February 2006; Published online 24 April 2006.

Abstract

The short arm of chromosome 8, 8p, is often rearranged in carcinomas, typically showing distal loss by unbalanced translocation. We analysed 8p rearrangements in 48 breast, pancreatic and colon cancer cell lines by fluorescence in situ hybridization (FISH) and array comparative genomic hybridization, with a tiling path of 0.2 Mb resolution over 8p12 and 1 Mb resolution over chromosome 8. Selected breast lines (MDA-MB-134, MDA-MB-175, MDA-MB-361, T-47D and ZR-75-1) were analysed further. Most cell lines showed loss of 8p distal to a break that was between 31 Mb (5' to NRG1) and the centromere, but the translocations were accompanied by variable amplifications, deletions and inversions proximal to this break. The 8p12 translocation in T-47D was flanked by an inversion of 4 Mb, with a 100 kb deletion at the proximal end. The dicentric t(8;11) in ZR-75-1 carries multiple rearrangements including interstitial deletions, a triplicated translocation junction between NRG1 and a fragment of 11q (unconnected to CCND1), and two separate amplifications, of FGFR1 and CCND1 . We conclude that if there is a tumour suppressor gene on 8p it may be near 31 Mb, for example WRN; but the complexity of 8p rearrangements suggests that they target various genes proximal to 31 Mb including NRG1 and the amplicon centred around ZNF703/FLJ14299.