Gene Expression
Finding Hidden Oncogenes in Chromosomal Regions
A review of A 1 Mb minimal amplicon at 8p11–12 in breast cancer identifies new candidate oncogenes.
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
Chromosomal aberrations have been identified as a hallmark of human cancer, with substantial evidence frequently implicating chromosome 8, and the 8p11–12 amplicon more specifically. In spite of the significance of this region, the related oncogene/s responsible for the aberration have not been identified, to date. Garcia and a team of researchers from the United Kingdom (2005) used home-brew, custom CGH microarrays covering 8p11–12 to analyze 33 primary breast tumors, 20 primary ovarian tumors, and 27 breast cancer cell lines. The team used Agilent’s Human 1A Oligo Microarrays to perform expression analysis of the genes in the region, finding that in most of the amplified cases, the genes within the amplicon boundaries were overexpressed. This research resulted in the identification of four new genes strongly correlated between amplification and overexpression, an indication that they may be the best candidate driver oncogenes
at 8p12.
Figure 1. Gene expression across the 8p11-12 region.
(a) Expression level of genes located at 8p11-12 assessed by rtq-PCR. Each row corresponds to one gene ordered according to its genomic position from the most distal one (top) to the most proximal one (bottom). Genes analysed by rtq-PCR and oligoarray are shown in bold font. The black bar on the right indicates the genes contained within the minimal region of amplification. Each column represents a sample. Samples are grouped according to whether they show no copy-number changes or amplification at 8p11-12. White frames delimit the genes within the amplicon in each sample. Log2 ratios are depicted in a color scale where red represents upregulation and green downregulation (note that it is the reverse to the CGH display where red conventionally represents loss). (b) Comparison of gene expression between samples showing no copy-number changes and amplification at 8p11-12 by rtq-PCR. Bars represent the normalized median log2 ratio for each group of samples. Asterisks indicate genes whose expression was significantly different between the two groups (P<0.05, Wilcoxon's rank-sum test). (c) Expression level of genes located at 8p11-12 assessed by expression oligo-microarray (layout as
described in a)
Title: A 1 Mb minimal amplicon at 8p11–12 in breast cancer identifies new candidate oncogenes.
Journal: Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18211-18216.
Authors: Maria J Garcia, Jessica C M Pole, Suet-Feung Chin, Andrew Teschendorff, Ali Naderi, Hilal Ozdag, Maria Vias, Tanja Kranjac, Tatiana Subkhankulova, Claire Paish, Ian Ellis, James D Brenton, Paul A W Edwards and Carlos Caldas.
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