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

• Main Authors: Ellis Ian O, Chin Suet-Feung, Pole Jessica CM, Cooke Susanna L, Caldas Carlos, Edwards Paul AW
• Format: Article
• Language: English
• Published: BMC 2008-10-01
• Series: BMC Cancer
• Online Access: http://www.biomedcentral.com/1471-2407/8/288

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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, <it>ARHGEF10 </it>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 <it>TUSC3</it>. A novel amplicon was found within 8p21.3 (19.1 Mb – 23.4 Mb) in two lines and one of 98 tumours.</p> <p>Conclusion</p> <p>The pattern of rearrangements seen on 8p may be a consequence of the high density of potential targets on this chromosome arm, and <it>ARHGEF10 </it>may be a new candidate tumour suppressor gene.</p>