Association of gene expression and genomic change, analysed using microarrays, with phenotype in breast carcinoma

• Main Author: Turton, Nicola
• Published: University of Leicester 2003
• Subjects: 616.99
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.697267

Breast cancer is the commonest malignancy to affect women and approximately 1 in 9 women (12 %) will develop the disease in developed countries (Burstein and Winer 2000). A major problem for treatment is the development of a drug resistant phenotype, whereby the tumour fails to respond to chemotherapy. This phenotype arises from altered gene expression in the resistant cells, which can occur by changes in transcription and/or genomic alteration. Other phenotypic properties of breast carcinoma cells may also arise in this way, and gene expression profiles can be linked to different breast tumour phenotypes, such as oestrogen receptor (ER) status, clinical tumour stage and tumour size (Martin et al., 2000). In this thesis cDNA microarrays were utilised to study both genomic amplification and RNA expression changes occurring in human breast carcinoma. These changes were related to phenotypic characteristics including a doxorubicin (Dox) resistant phenotype, hormone receptor status, tumour grade and type. Several gene clusters involving the development of resistance and the eventual Dox resistant phenotype in breast cancer cell lines were elucidated, associated with both these was the multi drug resistance 1 gene (ABCB1). Potential therapeutic targets in these cells e.g. the oxytocin receptor gene (OXTR) were also indicated. Regions of genomic amplification and specific genes were elucidated some of these have previously been described while others are novel. Some of the genomic changes were associated with tumour phenotype, for example gene amplification at chromosome 2p25 and 22qll were specific to lymph node positive tumours and 2 genes were consistently found amplified in these regions, LPIN1 and DGSI respectively. The findings of this study have contributed to the general understanding of genetic events occurring in breast cancer and associations between these changes and phenotype were suggested.