Project 6

1. Applicant

2. Topic

From genetic aberrations to therapy target structures: identification of initiating and promoting events in malignant melanoma

3. Short summary

Current cancer genome projects aim to identify therapy target structures by whole genome sequencing of primary cancers. We recently found that primary melanomas and disseminated melanoma cells rapidly diverge for chromosomal alterations as well as point mutations, which questions the relevance of primary melanomas as surrogate markers for systemic disease. In contrast, direct genetic analysis of disseminated melanoma cells may identify genes suitable as therapeutic targets particularly for the adjuvant setting. To narrow the regions of interest identified by our previous metaphase-CGH screen, we developed BAC-array CGH for high-resolution genome analysis of single cells. In the proposed project we will concentrate on specific regions located on several chromosomes that are characteristically altered in single, early-disseminated melanoma cells, as well as on regions that are shared between primary melanomas and disseminated melanoma cells. We will prepare a BAC array at tiling resolution of the selected regions, in order to identify the underlying genes. Since all melanoma cells were isolated within a prospective study design, survival analysis of the patients will be used to identify genes of clinical relevance for systemic progression. Finally, with the help of the consortium we will evaluate the molecular and cellular function of identified genes and determine their role as therapy targets for the adjuvant treatment of systemic melanoma.

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