title: Co-amplification of 8p12 and 11q13 in breast cancers is not the result of a single genomic event.
abstract: Epithelial cancers frequently have multiple amplifications, and particular amplicons tend to occur together. These co-amplifications have been suggested to result from amplification of pre-existing junctions between two chromosomes, that is, translocation junctions. We investigated this hypothesis for two amplifications frequent in breast cancer, at 8p12 and 11q13, which had been reported to be associated in Southern blot studies. We confirmed that both genomic amplification and expression of genes was correlated between the frequently-amplified regions of 8p and 11q, in array CGH and microarray expression data, supporting the importance of co-amplification. We examined by FISH the physical structure of co-amplifications that we had identified by array CGH, in five breast cancer cell lines (HCC1500, MDA-MB-134, MDA-MB-175, SUM44, and ZR-75-1), four breast tumors, and a pancreatic cancer cell line (SUIT2). We found a variety of arrangements: amplification of translocation junctions; entirely independent amplification of the two regions on separate chromosomes; and separate amplification of 8p and 11q sequences in distinct sites on the same rearranged chromosome. In this last arrangement, interphase nuclei often showed intermingling of FISH signals from 8p12 and 11q13, giving a false impression that the sequences were interdigitated. We conclude that co-amplification of the main 8p and 11q amplicons in breast tumors is not usually the result of a preceding translocation event but most likely reflects selection of clones that have amplified both loci. This article contains supplementary material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
authors.affiliation: Hutchison-MRC Research Centre, Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Paterson
authors.forename: Jessica C M
authors.initials: JC
authors.lastname: Pole
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Blood
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Garcia
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Cooke
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Teschendorff
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Suet-Feung
authors.initials: SF
authors.lastname: Chin
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.forename: Paul A W
authors.initials: PA
authors.lastname: Edwards
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005784:Gene Amplification; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D009363:Neoplasm Proteins