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Comprehensive Analysis of the genomic evolution of clonal populations in the progression of hormone sensitive prostate and breast cancers

Research Project
 | 
01.07.2011
 - 30.06.2013

This study has two main focuses: first, the detection of novel gene fusions and second, the further development and application of a technology for the clonal analysis of solid tumor samples. The methodology relies on a unique combination of flow-sorting clonal tumor cell populations and the genomic characterization of the resulting populations by array-CGH or targeted sequencing. Due to the evidentiary success of this innovative methodology, we plan to apply it to a carefully selected, unique prostate and breast cancer cohort. For this purpose, multiple samples (primary/recurrence or primary/metastases) from single patients will be subjected to clonal flow-sorting and genomic analyses. Rigorous bioinformatic analyses and knowledge mining will be applied to the resulting data, followed by clinical validation using tissue microarrays and functional experiments in established cell line models. We are convinced that appliance of this cutting-edge technique to these unique samples will lead to novel and unprecedented results about the evolution of distinct clonal populations within a tumor and their response to the selective pressure caused by the therapeutic regimen. Further, inclusion of metastases from the same patients will allow us to interrogate which clonal tumor population was able to metastasize and how it propagated at the new anatomical site. We are confident that results from this proposed study can be translated into the clinics and can contribute to the development of personalized medicine in cancer treatment.

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Lukas Bubendorf

Principal Investigator