High-resolution array CGH clarifies events occurring on 8p in carcinogenesis

Cooke, S. L. , Pole, J. C.M., Chin, S.-F., Ellis, I. O., Caldas, C. and Edwards, P. A.W. (2008) High-resolution array CGH clarifies events occurring on 8p in carcinogenesis. BMC Cancer, 8, 288. (doi: 10.1186/1471-2407-8-288) (PMID:18840272) (PMCID:PMC2576333)

Abstract

Background: Rearrangement of the short arm of chromosome 8 (8p) is very common in epithelial cancers such as breast cancer. Usually there is an unbalanced translocation breakpoint in 8p12 (29.7 Mb – 38.5 Mb) with loss of distal 8p, sometimes with proximal amplification of 8p11-12. Rearrangements in 8p11-12 have been investigated using high-resolution array CGH, but the first 30 Mb of 8p are less well characterised, although this region contains several proposed tumour suppressor genes. Methods: We analysed the whole of 8p by array CGH at tiling-path BAC resolution in 32 breast and six pancreatic cancer cell lines. Regions of recurrent rearrangement distal to 8p12 were further characterised, using regional fosmid arrays. FISH, and quantitative RT-PCR on over 60 breast tumours validated the existence of similar events in primary material. Results: We confirmed that 8p is usually lost up to at least 30 Mb, but a few lines showed focal loss or copy number steps within this region. Three regions showed rearrangements common to at least two cases: two regions of recurrent loss and one region of amplification. Loss within 8p23.3 (0 Mb – 2.2 Mb) was found in six cell lines. Of the genes always affected, ARHGEF10 showed a point mutation of the remaining normal copies in the DU4475 cell line. Deletions within 12.7 Mb – 19.1 Mb in 8p22, in two cases, affected TUSC3. A novel amplicon was found within 8p21.3 (19.1 Mb – 23.4 Mb) in two lines and one of 98 tumours. Conclusion: The pattern of rearrangements seen on 8p may be a consequence of the high density of potential targets on this chromosome arm, and ARHGEF10 may be a new candidate tumour suppressor gene.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cooke, Dr Susie
• Authors: Cooke, S. L., Pole, J. C.M., Chin, S.-F., Ellis, I. O., Caldas, C., and Edwards, P. A.W.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: BMC Cancer
• Publisher: BioMed Central
• ISSN: 1471-2407
• ISSN (Online): 1471-2407
• Copyright Holders: Copyright © 2008 Cooke et al.
• First Published: First published in BMC Cancer 8:288
• Publisher Policy: Reproduced under a Creative Commons License