Lars O. Baumbusch

The main focus of this project group is to explore the genomic characteristics of disseminated tumor cells in breast cancer and to allocate their relevance to clinical parameters. The critical step in breast cancer progression is the establishment of metastasis to distant organs. Circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells (DTC) in secondary organs like bone marrow are considered to be rare members among the cellular population of primary tumor cells. In several studies it has been demonstrated that the presence of these cells is an independent prognostic factor and detection of DTC identifies patients with less favorable clinical outcome. However, we still lack knowledge of the genomic characteristics of DTC and how to target these cells. A reason for this limitation has been a deficiency of procedures allowing high-resolution analyses of CTC/DTC, including DNA-copy number changes. Due to the implementation of a state-of-the-art technique, called single cell array comparative genomic hybridization (SCaCGH), we are finally able to perform in-depth analysis of occult circulating tumor cells on various high density array platforms. Further, new tools for detection and characterization of CTC/DTC including qRT-PCR have been developed. Genotyping and phenotyping of occult tumor cells will provide information to better understand tumor initiation, tumor heterogeneity, and subsequent metastasis formation. Using novel bioinformatic and biostatistical tools studied in connection with a detailed primary tumor analysis, we wish to identify biological markers and genes responsible for the capacity of cancer cells to metastasize. This may be clinically useful as evidence for an early occult spread of tumor cells, as a relevant prognostic factor, and finally, permit direct exploration of markers for targeted treatment.

The project is an integrative part of the Breast Cancer study (headed by Bjørn Naume) in the Micrometastasis project ongoing at the Norwegian Radium Hospital. The work is performed in close collaboration between the Dep. of Pathology and the Dep. of Genetics.

The project is supported by DISMAL. The main objective of DISMAL is to improve specificity and sensitivity of current platforms for DTC (disseminated tumor cells) detection in patients with epithelial tumors. The Goal is to identify novel markers at the DNA, RNA or protein level that allows a more precise detection of DTC with a high risk for metastatic progression.

Information to the various subprojects

Prosjektbeskrivelse på norsk