title: A 1 Mb minimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes.
abstract: Amplification of 8p11-12 is a well-known alteration in human breast cancers but the driving oncogene has not been identified. We have developed a high-resolution comparative genomic hybridization array covering 8p11-12 and analysed 33 primary breast tumors, 20 primary ovarian tumors and 27 breast cancer cell lines. Expression analysis of the genes in the region was carried out by using real-time quantitative PCR and/or oligo-microarray profiling. In all, 24% (8/33) of the breast tumors, 5% (1/20) of the ovary tumors and 15% (4/27) of the cell lines showed 8p11-12 amplification. We identified a 1 Mb segment of common amplification that excludes previously proposed candidate genes. Some of the amplified genes did not show overexpression, whereas for others, overexpression was not specifically attributable to amplification. The genes FLJ14299, C8orf2, BRF2 and RAB11FIP, map within the 8p11-12 minimal amplicon, two have a putative function consistent with an oncogenic role, these four genes showed a strong correlation between amplification and overexpression and are therefore the best candidate driver oncogenes at 8p12.
authors.affiliation: Department of Oncology, Hutchison/MRC Research Centre, Cancer Genomics Program, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Garcia
authors.forename: Jessica C M
authors.initials: JC
authors.lastname: Pole
authors.forename: Suet-Feung
authors.initials: SF
authors.lastname: Chin
authors.forename: Andrew
authors.initials: A
authors.lastname: Teschendorff
authors.forename: Ali
authors.initials: A
authors.lastname: Naderi
authors.forename: Hilal
authors.initials: H
authors.lastname: Ozdag
authors.forename: Maria
authors.initials: M
authors.lastname: Vias
authors.forename: Tanja
authors.initials: T
authors.lastname: Kranjac
authors.forename: Tatiana
authors.initials: T
authors.lastname: Subkhankulova
authors.forename: Claire
authors.initials: C
authors.lastname: Paish
authors.forename: Ian
authors.initials: I
authors.lastname: Ellis
authors.forename: James D
authors.initials: JD
authors.lastname: Brenton
authors.forename: Paul A W
authors.initials: PA
authors.lastname: Edwards
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction