High resolution genome analyses in breast cancer

Breast cancer represents a collection of tumours with widely different behaviour and clinical outcome. Genomic instability and in particular chromosomal instability, in terms of numerical aberrations (aneuploidy) and structural rearrangements (gene amplifications, deletions and translocations), is likely to be essential and rate limiting for tumour progression. Defects in cell cycle control play a central role in chromosomal destabilization and genomic instability. The aim of this project is to perform high resolution genome analyses of breast tumours and to correlate genomic and cell cycle abnormalities with clinical behaviour and tumour aggressiveness. Since the group of Prof. A. Zetterberg has access to a unique combination of techniques (ROMA and QM-FISH) and a unique tumour bank of tumour samples classified on the basis of clinical stage (size and lymph node status), morphology (grade and type), overall ploidy status (highly aneuploid vs. pseudo-diploid), proliferation index (S-phase fraction and/or cyclin A- level), type of therapy, distant metastasis free survival and overall survival, targeted analyses of defined subgroups of tumours are realizable. In this project we will work on the following subtopics: 1. Global search for copy number changes in the genome with the combination of two newly developed techniques for the high resolution analysis of the genome: a) ROMA (representational oligonucleotide microarray analysis) and b) QM-FISH (quantitative multigene fluorescence in situ hybridization) 2. Characterization of breast cancers with gene amplification by ROMA and QM-FISH and screening of these tumours for their complexity of 17q rearrangements particularly with respect to her-2/neu 3. Screening of tumour samples for their abnormal cyclin E expression pattern during the cell cycle by a technique developed in A. Zetterbergs laboratory, and to correlate this abnormality with chromosomal instability.