Vinsamlegast notið þetta auðkenni þegar þið vitnið til verksins eða tengið í það: http://hdl.handle.net/1946/5363
Genomic and expression analysis at the 8p12-p11 amplified region in breast cancer. Identifying potential target genes of the amplification
Mögnun og genatjáning á litningasvæði 8p12-p11 í brjóstaæxlum. Líkleg markgen mögnunarinnar tilgreind
Breast cancer is the most frequent cancer in women in Western Europe. It is a heterogeneous disease and mainly the consequence of alterations in environmental, genetic and epigenetic factors. Alterations in the genetic material of cells can drive the progressive transformation of normal cells into highly malignant tumour cells. Amplification at a chromosomal region containing oncogenes(s) gives cells strong selective advantage. The amplification at 8p12-p11 is a well known alteration in breast cancer and has been linked to poor prognosis. Several research groups have analysed the region with the aim of identifying the target gene(s) that drives the amplification. Despite that, the definite target gene(s) has not been identified yet. The aims of this study were to map the 8p12-p11 amplified region in breast tumours and analyse protein expression of genes at the region to identify potential target genes. Four criteria were set for a gene to be considered a likely target gene. In breast tumours, the gene had to be overexpressed when amplified, the overexpressed gene had to show correlation between protein expression and DNA copy number and protein expression of the genes had to correlate with mRNA expression. Also, the protein encoded by the gene had to be expressed at a higher level in at least 3 of 4 cell lines with amplification of the gene than in cell lines and primary cells without the amplification. Using array-CGH data from available databank including the DNA copy number in breast samples, the minimal region of amplification was mapped as a 1.6 Mb region where 20 known protein coding genes reside. Using array-GEx results from the same databank, correlation between the DNA copy number and mRNA level revealed thirteen genes as overexpressed when amplified. Protein expression analysis in breast tumours, breast cell lines and primary epithelial cells indicated seven of these genes as the most likely candidate target genes of the 8p12-p11 amplified region based on that they met all the criteria.