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  • Oncogenomics
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High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation

Oncogene volume 25, pages 5693–5706 (2006)Cite this article

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.

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Acknowledgements

We thank Huai-En Huang, Rachel Lyman, Nicholas J Roberts, Joanne M Staines, Melody Tabiner, and Katherine Williams for contributing to the FISH data and cell culture. Supported by Cancer Research UK, Biotechnology and Biological Sciences Research Council (BBSRC), Breast Cancer Campaign, Wellbeing, Medical Research Council (studentship for SLC), Cambridge Commonwealth Trust (studentships for AEA, KAB) and Sackler Fund (KAB).

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Author notes

  1. C Courtay-Cahen

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

  2. A E Alsop

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

  3. D M L Tse

    Present address: University of Cambridge Clinical School, Hills Road, Cambridge, UK

Authors and Affiliations

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

    J C M Pole, C Courtay-Cahen, M J Garcia, K A Blood, S L Cooke, A E Alsop, D M L Tse, C Caldas & P A W Edwards

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Correspondence to P A W Edwards.

Additional information

Note:

Further analysis of 8p12 amplicons was recently published by Gelsi-Boyer et al., 2005. Mole Cancer Res.

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Pole, J., Courtay-Cahen, C., Garcia, M. et al. High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation. Oncogene 25, 5693–5706 (2006). https://doi.org/10.1038/sj.onc.1209570

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