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

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.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.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.Rearrangements of the short arm of chromosome 8 (8p) are one of the most common genetic events in breast [1-3], pancreatic [4] and many other epithelial carcinomas [5]. Although these rearrangements have been studied using a variety of techniques, including cytogenetics, CGH (comparative genomic hybridisation), array CGH and LOH (loss of heterozygosity) analysis [1-4], their resolution, with the exception of studies on 8p12 which are discussed below, has been insufficient to provide a feasibly small number of candidate genes for further analysis.Loss of heterozygosity (LOH) studies suggest that there are at least three tumour suppressor genes on 8p, in bands 8p23, 8p22, and 8p21, lost in several epithelial tumour types [6-8]. The highest resolution of these studies is just over 1 Mb, showing that bladder tumours have a common region of LO